Skip to main content
Top
Published in: Cancer Immunology, Immunotherapy 2/2005

01-02-2005 | Review

Immunoprevention and immunotherapy of cancer in ageing

Authors: Mauro Provinciali, Arianna Smorlesi

Published in: Cancer Immunology, Immunotherapy | Issue 2/2005

Login to get access

Abstract

Over the last few years there has been a growing interest in geriatric oncology, mainly because of the evidence that advanced age is the greatest risk factor for the development of cancer and that, since the elderly population is rapidly expanding, so too will the number of cancer patients. This forecast necessitates the development of new and more specific strategies for the prevention and cure of cancer in the elderly and as a result an ever-increasing need for oncologists, geriatricians and researchers to work closely together. The increased incidence of cancer in elderly people has been related to the age-associated changes occurring in the immune system, the so-called immunosenescence. This phenomenon is best characterised by a remodelling of the immune system, which appears early on and progresses throughout a person’s life and mainly involves a decrease in cellular functions. This review aims to provide a rationale for the development of specific immunotherapeutic and immunopreventive regimens for the elderly. We also include a discussion on the influence that immunosenescence has on the growth of tumours and the effectiveness of immunogene therapy and cancer vaccination following a brief analysis of the age-related alterations of the cell populations involved in antitumour immunity.
Literature
1.
go back to reference Thoman ML, Weigle WO (1989) The cellular and subcellular bases of immunosenescence. In: Dixon FJ (ed) Advances in immunology, vol 46. Academic, San Diego, p 221 Thoman ML, Weigle WO (1989) The cellular and subcellular bases of immunosenescence. In: Dixon FJ (ed) Advances in immunology, vol 46. Academic, San Diego, p 221
2.
go back to reference Miller RA (1996) The ageing immune system: primer and prospectus. Science 273:70PubMed Miller RA (1996) The ageing immune system: primer and prospectus. Science 273:70PubMed
3.
go back to reference Pawelec G, Solana R (1997) Immunosenescence. Trend Immunol 11:514 Pawelec G, Solana R (1997) Immunosenescence. Trend Immunol 11:514
4.
go back to reference Burns EA, Goodwin JS (1998) Immunological changes of aging. In: Balducci L, Lyman GH, Ershler WB (eds) Comprehensive geriatric oncology. Harwood Academic Publishers, The Netherlands, p 213 Burns EA, Goodwin JS (1998) Immunological changes of aging. In: Balducci L, Lyman GH, Ershler WB (eds) Comprehensive geriatric oncology. Harwood Academic Publishers, The Netherlands, p 213
5.
go back to reference Hoffmann JA, Kafatos FC, Janeway CA Jr, Ezekowitz RAB (1999) Phylogenetic perspectives in innate immunity. Science 284:1313CrossRefPubMed Hoffmann JA, Kafatos FC, Janeway CA Jr, Ezekowitz RAB (1999) Phylogenetic perspectives in innate immunity. Science 284:1313CrossRefPubMed
6.
go back to reference Fabris E, Mocchegiani, Provinciali M (1994) Plasticity of neuroendocrine-immune interactions during aging. In: Berczi I, Szèlenyi J (eds) Advances in psychoneuroimmunology. Plenum, New York, p 331 Fabris E, Mocchegiani, Provinciali M (1994) Plasticity of neuroendocrine-immune interactions during aging. In: Berczi I, Szèlenyi J (eds) Advances in psychoneuroimmunology. Plenum, New York, p 331
7.
go back to reference George AJ, Ritter MA (1996) Thymic involution with ageing: obsolescence or good housekeeping? Immunol Today 17:267CrossRefPubMed George AJ, Ritter MA (1996) Thymic involution with ageing: obsolescence or good housekeeping? Immunol Today 17:267CrossRefPubMed
8.
go back to reference Solana R, Pawelec G (1998) Molecular and cellular basis of immunosenescence. Mech Ageing Dev 102:115CrossRefPubMed Solana R, Pawelec G (1998) Molecular and cellular basis of immunosenescence. Mech Ageing Dev 102:115CrossRefPubMed
10.
go back to reference Rink L, Cakman I, Kirchner H (1998) Altered cytokine production in the elderly. Mech Ageing Dev 102:199CrossRefPubMed Rink L, Cakman I, Kirchner H (1998) Altered cytokine production in the elderly. Mech Ageing Dev 102:199CrossRefPubMed
11.
go back to reference Miller JP, Allman D (2003) The decline in B lymphopoiesis in aged mice reflects loss of very early B-lineage precursors. J Immunol 171:2326PubMed Miller JP, Allman D (2003) The decline in B lymphopoiesis in aged mice reflects loss of very early B-lineage precursors. J Immunol 171:2326PubMed
12.
go back to reference Sailey RW, Eun SY, Russell CE, Vogel LA (2001) B cells of aged mice show decreased expansion in response to antigen, but are normal in effector function. Cell Immunol 214:99CrossRefPubMed Sailey RW, Eun SY, Russell CE, Vogel LA (2001) B cells of aged mice show decreased expansion in response to antigen, but are normal in effector function. Cell Immunol 214:99CrossRefPubMed
13.
go back to reference Ershler WB, Moore AL, Socinski MA (1984) Influenza and aging: age-related changes and the effects of thymosin on the antibody response to influenza vaccine. J Clin Immunol 4:445PubMed Ershler WB, Moore AL, Socinski MA (1984) Influenza and aging: age-related changes and the effects of thymosin on the antibody response to influenza vaccine. J Clin Immunol 4:445PubMed
14.
go back to reference Kishimoto S, Tomino S, Mitsuya H, Nishimura H (1982) Age-related decrease in frequencies of B-cell precursors and specific helper T cells involved in the IgG anti-tetanus toxoid antibody production in humans. Clin Immunol Immunopathol 25:1CrossRefPubMed Kishimoto S, Tomino S, Mitsuya H, Nishimura H (1982) Age-related decrease in frequencies of B-cell precursors and specific helper T cells involved in the IgG anti-tetanus toxoid antibody production in humans. Clin Immunol Immunopathol 25:1CrossRefPubMed
15.
go back to reference Lutz MB, Schuler G (2002) Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity? Trends Immunol 23(9):445CrossRefPubMed Lutz MB, Schuler G (2002) Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity? Trends Immunol 23(9):445CrossRefPubMed
16.
go back to reference Effros RB, Walford RL (1984) The effect of age on the antigen-presenting mechanism in limiting diluition precursor cell frequency analysis. Cell Immunol 88:531PubMed Effros RB, Walford RL (1984) The effect of age on the antigen-presenting mechanism in limiting diluition precursor cell frequency analysis. Cell Immunol 88:531PubMed
17.
go back to reference Miller C, Kelsoe G, Han S (1994) Lack of B7-2 expression in the germinal centers of aged mice. Ageing Immunol Infect Dis 5:249 Miller C, Kelsoe G, Han S (1994) Lack of B7-2 expression in the germinal centers of aged mice. Ageing Immunol Infect Dis 5:249
18.
go back to reference Donnini A, Argentati K, Mancini R, Smorlesi A, Bartozzi B, Bernardini G, Provinciali M (2002) Phenotype antigen-presenting capacity, and migration of antigen-presenting cells in young and old age. Exp Gerontol 37:1097CrossRefPubMed Donnini A, Argentati K, Mancini R, Smorlesi A, Bartozzi B, Bernardini G, Provinciali M (2002) Phenotype antigen-presenting capacity, and migration of antigen-presenting cells in young and old age. Exp Gerontol 37:1097CrossRefPubMed
19.
go back to reference Provinciali M, Donnini A, Re F (2004) MHC-unrestricted cytotoxicity in ageing. In: Straub RH, Mocchegiani E (eds) The neuroendocrine immune network in ageing. Neuroimmune biology, vol 4. Elsevier, Amsterdam Provinciali M, Donnini A, Re F (2004) MHC-unrestricted cytotoxicity in ageing. In: Straub RH, Mocchegiani E (eds) The neuroendocrine immune network in ageing. Neuroimmune biology, vol 4. Elsevier, Amsterdam
20.
go back to reference Carrard G, Bulteau AL, Petropoulos I, Friguet B (2002) Impairment of proteasome structure and function in aging Int J Biochem Clee Biol 34:1461CrossRef Carrard G, Bulteau AL, Petropoulos I, Friguet B (2002) Impairment of proteasome structure and function in aging Int J Biochem Clee Biol 34:1461CrossRef
21.
go back to reference Mishto M, Santoro A, Bellavista E, Bonafe M, Monti D, Franceschi C (2003) Immunoproteasomes and immunosenescence. Ageing Res Rev 2:419CrossRefPubMed Mishto M, Santoro A, Bellavista E, Bonafe M, Monti D, Franceschi C (2003) Immunoproteasomes and immunosenescence. Ageing Res Rev 2:419CrossRefPubMed
22.
go back to reference Lung TL, Saurwein-Teissl M, Parson W, Schonitzer D, Grubeck-Loebenstein B (2000) Unimpaired dendritic cells can be derived from monocytes in old age and can mobilize residual function in senescent T cells. Vaccine 18:1606CrossRefPubMed Lung TL, Saurwein-Teissl M, Parson W, Schonitzer D, Grubeck-Loebenstein B (2000) Unimpaired dendritic cells can be derived from monocytes in old age and can mobilize residual function in senescent T cells. Vaccine 18:1606CrossRefPubMed
23.
go back to reference Steger MM, Maczek C, Grubeck-Loebenstein B (1996a) Morphologically and functionally intact dendritic cells can be derived from the peripheral blood of aged individuals. Clin Exp Immunol 105:544CrossRefPubMed Steger MM, Maczek C, Grubeck-Loebenstein B (1996a) Morphologically and functionally intact dendritic cells can be derived from the peripheral blood of aged individuals. Clin Exp Immunol 105:544CrossRefPubMed
24.
go back to reference Akira S, Takeda K, Kaisho T (2001) Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2:675CrossRefPubMed Akira S, Takeda K, Kaisho T (2001) Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2:675CrossRefPubMed
25.
go back to reference Renshaw M, Rockwell J, Engleman C, Gewirtz A, Katz J, Sambhara S (2002) Cutting edge: impaired Toll-like receptor expression and function in ageing. J Immunol 169:4697PubMed Renshaw M, Rockwell J, Engleman C, Gewirtz A, Katz J, Sambhara S (2002) Cutting edge: impaired Toll-like receptor expression and function in ageing. J Immunol 169:4697PubMed
26.
go back to reference Franc NC, White K, Ezekowitz RA (1999) Phagocytosis and development: back to the future. Curr Opin Immunol 11:47CrossRefPubMed Franc NC, White K, Ezekowitz RA (1999) Phagocytosis and development: back to the future. Curr Opin Immunol 11:47CrossRefPubMed
27.
go back to reference Ohashi K, Burkart V, Flohe S, Kolb H (2000) Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex. J Immunol 164:558PubMed Ohashi K, Burkart V, Flohe S, Kolb H (2000) Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex. J Immunol 164:558PubMed
28.
go back to reference Castle S, Uyemura K, Wong W, Modlin RL, Effros R (1997) Evidence of enhanced type 2 immune response and impaired up-regulation of a type 1 response in frail elderly nursing home residents. Mech Ageing Dev 94:7CrossRefPubMed Castle S, Uyemura K, Wong W, Modlin RL, Effros R (1997) Evidence of enhanced type 2 immune response and impaired up-regulation of a type 1 response in frail elderly nursing home residents. Mech Ageing Dev 94:7CrossRefPubMed
29.
go back to reference Frasca D, Pucci S, Goso C, Barattini P, Barile S, Pioli C, Doria G (1997) Regulation of cytokine production in aging: use of recombinant cytokines to upregulate mitogen-stimulated spleen cells. Mech Ageing Dev 93:157CrossRefPubMed Frasca D, Pucci S, Goso C, Barattini P, Barile S, Pioli C, Doria G (1997) Regulation of cytokine production in aging: use of recombinant cytokines to upregulate mitogen-stimulated spleen cells. Mech Ageing Dev 93:157CrossRefPubMed
30.
go back to reference Lio D, D’Anna C, Gervasi F, Scola L, Potestio M, Di Lorenzo G, Listi F, Colombo A, Candore G, Caruso C (1998) Interleukin-12 release by mitogen-stimulated mononuclear cells in the elderly. Mech Ageing Dev 102:211CrossRefPubMed Lio D, D’Anna C, Gervasi F, Scola L, Potestio M, Di Lorenzo G, Listi F, Colombo A, Candore G, Caruso C (1998) Interleukin-12 release by mitogen-stimulated mononuclear cells in the elderly. Mech Ageing Dev 102:211CrossRefPubMed
31.
go back to reference Ershler W, Longo DL (1997) Aging and cancer: issues of basic and clinical science. J Natl Cancer Inst 8:1489CrossRef Ershler W, Longo DL (1997) Aging and cancer: issues of basic and clinical science. J Natl Cancer Inst 8:1489CrossRef
32.
go back to reference Provinciali M, Argentati K, Tibaldi A (2000) Efficacy of cancer gene therapy in aging: adenocarcinoma cells engineered to release IL-2 are rejected but do not induce tumor specific immune memory in old mice. Gene Ther 7:624CrossRefPubMed Provinciali M, Argentati K, Tibaldi A (2000) Efficacy of cancer gene therapy in aging: adenocarcinoma cells engineered to release IL-2 are rejected but do not induce tumor specific immune memory in old mice. Gene Ther 7:624CrossRefPubMed
33.
go back to reference Bar-Eli M, Gallily R (1979) Age-dependent macrophage functions in New Zealand black mice. Cell Immunol 45:309PubMed Bar-Eli M, Gallily R (1979) Age-dependent macrophage functions in New Zealand black mice. Cell Immunol 45:309PubMed
34.
go back to reference Jaroslow BN, Larrick JW (1973) Clearance of foreign red cells from the blood of ageing mice. Mech Ageing Dev 2:23CrossRefPubMed Jaroslow BN, Larrick JW (1973) Clearance of foreign red cells from the blood of ageing mice. Mech Ageing Dev 2:23CrossRefPubMed
35.
go back to reference Sadeghi HM, Schnelle JF, Thoma JK, Nishanian P, Fahey JL (1999) Phenotypic and functional characteristics of circulating monocytes of elderly persons. Exp Gerontol 34:959CrossRefPubMed Sadeghi HM, Schnelle JF, Thoma JK, Nishanian P, Fahey JL (1999) Phenotypic and functional characteristics of circulating monocytes of elderly persons. Exp Gerontol 34:959CrossRefPubMed
36.
go back to reference O’Mahony L, Holland J, Jackson J, Feighery C, Hennessy TP, Mealy K (1998) Quantitative intracellular cytokine measurement: age-related changes in proinflammatory cytokine production. Clin Exp Immunol 113:213CrossRefPubMed O’Mahony L, Holland J, Jackson J, Feighery C, Hennessy TP, Mealy K (1998) Quantitative intracellular cytokine measurement: age-related changes in proinflammatory cytokine production. Clin Exp Immunol 113:213CrossRefPubMed
37.
go back to reference Ahluwalia N, Mastro AM, Ball R, Miles MP, Rajendra R, Handte G (2001) Cytokine production by stimulated mononuclear cells did not change with ageing in apparently healthy, well-nourished women. Mech Ageing Dev 122:1269CrossRefPubMed Ahluwalia N, Mastro AM, Ball R, Miles MP, Rajendra R, Handte G (2001) Cytokine production by stimulated mononuclear cells did not change with ageing in apparently healthy, well-nourished women. Mech Ageing Dev 122:1269CrossRefPubMed
38.
go back to reference McLachlan JA, Serkin CD, Morrey KM, Bakouche O (1995) Antitumoral properties of aged human monocytes. J Immunol 154:832PubMed McLachlan JA, Serkin CD, Morrey KM, Bakouche O (1995) Antitumoral properties of aged human monocytes. J Immunol 154:832PubMed
39.
go back to reference Corsini E, Battaini F, Lucchi L, Marinovich M, Racchi M, Govoni S, Galli CL (1999) Reduction of transendothelial migration of mononuclear cells in interferon-beta1b-treated multiple sclerosis patients. Ann Neurol 46:435CrossRefPubMed Corsini E, Battaini F, Lucchi L, Marinovich M, Racchi M, Govoni S, Galli CL (1999) Reduction of transendothelial migration of mononuclear cells in interferon-beta1b-treated multiple sclerosis patients. Ann Neurol 46:435CrossRefPubMed
40.
go back to reference Khare V, Sodhi A, Singh SM (1996) Effect of ageing on the tumoricidal functions of murine peritoneal macrophages. Nat Immun 15:285PubMed Khare V, Sodhi A, Singh SM (1996) Effect of ageing on the tumoricidal functions of murine peritoneal macrophages. Nat Immun 15:285PubMed
41.
go back to reference Wallace PK, Eisenstein TK, Meissler JJ Jr, Morahan PS (1995) Decreases in macrophage mediated antitumor activity with aging. Mech Ageing Dev 77:169CrossRefPubMed Wallace PK, Eisenstein TK, Meissler JJ Jr, Morahan PS (1995) Decreases in macrophage mediated antitumor activity with aging. Mech Ageing Dev 77:169CrossRefPubMed
42.
go back to reference Herrero C, Marques L, Lloberas J, Celada A (2001) IFN-gamma-dependent transcription of MHC class II IA is impaired in macrophages from aged mice. J Clin Invest 107:485PubMed Herrero C, Marques L, Lloberas J, Celada A (2001) IFN-gamma-dependent transcription of MHC class II IA is impaired in macrophages from aged mice. J Clin Invest 107:485PubMed
43.
go back to reference Cavallo F, Giovarelli M, Gulino A, Vacca A, Stoppacciaro A, Modesti A, Forni G (1992) Role of neutrophils and CD4+ T lymphocytes in the primary and memory response to nonimmunogenic murine mammary adenocarcinoma made immunogenic by IL-2 gene. J Immunol 149:3627PubMed Cavallo F, Giovarelli M, Gulino A, Vacca A, Stoppacciaro A, Modesti A, Forni G (1992) Role of neutrophils and CD4+ T lymphocytes in the primary and memory response to nonimmunogenic murine mammary adenocarcinoma made immunogenic by IL-2 gene. J Immunol 149:3627PubMed
44.
go back to reference Cavallo F, Signorelli P, Giovarelli M, Musiani P, Modesti A, Brunda MJ, Colombo MP, Forni G (1997) Antitumor efficacy of adenocarcinoma cells engineered to produce interleukin 12 (IL-12) or other cytokines compared with exogenous IL-12. J Natl Cancer Inst 89(14):1049CrossRefPubMed Cavallo F, Signorelli P, Giovarelli M, Musiani P, Modesti A, Brunda MJ, Colombo MP, Forni G (1997) Antitumor efficacy of adenocarcinoma cells engineered to produce interleukin 12 (IL-12) or other cytokines compared with exogenous IL-12. J Natl Cancer Inst 89(14):1049CrossRefPubMed
45.
go back to reference Angelis P, Scharf S, Christophidis N (1997) Effects of age on neutrophil function and its relevance to bacterial infections in the elderly. J Clin Lab Immunol 49:33PubMed Angelis P, Scharf S, Christophidis N (1997) Effects of age on neutrophil function and its relevance to bacterial infections in the elderly. J Clin Lab Immunol 49:33PubMed
46.
go back to reference Born J, Uthgenannt D, Dodt C, Nunninghoff D, Ringvolt E, Wagner T, Fehm HL (1995) Cytokine production and lymphocyte subpopulations in aged humans: an assessment during nocturnal sleep. Mech Ageing Dev 84:113CrossRefPubMed Born J, Uthgenannt D, Dodt C, Nunninghoff D, Ringvolt E, Wagner T, Fehm HL (1995) Cytokine production and lymphocyte subpopulations in aged humans: an assessment during nocturnal sleep. Mech Ageing Dev 84:113CrossRefPubMed
47.
go back to reference Chatta GS, Andrews RG, Rodger E, Schrag M, Hammond WP, Dale DC (1993) Hematopoietic progenitors and ageing: alterations in granulocytic precursors and responsiveness to recombinant human G-CSF, GM-CSF, and IL-3. J Gerontol 48:M207PubMed Chatta GS, Andrews RG, Rodger E, Schrag M, Hammond WP, Dale DC (1993) Hematopoietic progenitors and ageing: alterations in granulocytic precursors and responsiveness to recombinant human G-CSF, GM-CSF, and IL-3. J Gerontol 48:M207PubMed
48.
go back to reference MacGregor RR, Shalit M (1990) Neutrophil function in healthy elderly subjects. J Gerontol 45:M55–60PubMed MacGregor RR, Shalit M (1990) Neutrophil function in healthy elderly subjects. J Gerontol 45:M55–60PubMed
49.
go back to reference Phair JP, Kauffman CA, Bjornson A, Gallagher J, Adams L, Hess EV (1978) Host defenses in the aged: evaluation of components of the inflammatory and immune responses. J Infect Dis 138:67PubMed Phair JP, Kauffman CA, Bjornson A, Gallagher J, Adams L, Hess EV (1978) Host defenses in the aged: evaluation of components of the inflammatory and immune responses. J Infect Dis 138:67PubMed
50.
go back to reference Corberand J, Ngyen F, Laharrague P, Fontanilles AM, Gleyzes B, Gyrard E, Senegas C (1981) Polymorphonuclear functions and ageing in humans. J Am Geriatr Soc 29:391PubMed Corberand J, Ngyen F, Laharrague P, Fontanilles AM, Gleyzes B, Gyrard E, Senegas C (1981) Polymorphonuclear functions and ageing in humans. J Am Geriatr Soc 29:391PubMed
51.
go back to reference McLaughlin B, O’Malley K, Cotter TG (1986) Age-related differences in granulocyte chemotaxis and degranulation. Clin Sci (Lond) 70:59 McLaughlin B, O’Malley K, Cotter TG (1986) Age-related differences in granulocyte chemotaxis and degranulation. Clin Sci (Lond) 70:59
52.
go back to reference Antonaci S, Jirillo E, Ventura MT, Garofalo AR, Bonomo L (1984) Non-specific immunity in ageing: deficiency of monocyte and polymorphonuclear cell-mediated functions. Mech Ageing Dev 24:367CrossRefPubMed Antonaci S, Jirillo E, Ventura MT, Garofalo AR, Bonomo L (1984) Non-specific immunity in ageing: deficiency of monocyte and polymorphonuclear cell-mediated functions. Mech Ageing Dev 24:367CrossRefPubMed
53.
go back to reference Charpentier B, Fournier C, Fries D, Mathieu D, Noury J, Bach JF (1981) Immunological studies in human ageing. I. In vitro functions of T cells and polymorphs. J Clin Lab Immunol 5:87PubMed Charpentier B, Fournier C, Fries D, Mathieu D, Noury J, Bach JF (1981) Immunological studies in human ageing. I. In vitro functions of T cells and polymorphs. J Clin Lab Immunol 5:87PubMed
54.
go back to reference Corberand JX, Laharrague PF, Fillola G (1986) Neutrophils are normal in normal aged humans. J Leukoc Biol 40:333PubMed Corberand JX, Laharrague PF, Fillola G (1986) Neutrophils are normal in normal aged humans. J Leukoc Biol 40:333PubMed
55.
go back to reference Lipschitz DA, Udupa KB, Boxer LA (1988) The role of calcium in the age-related decline of neutrophil function. Blood 71:659PubMed Lipschitz DA, Udupa KB, Boxer LA (1988) The role of calcium in the age-related decline of neutrophil function. Blood 71:659PubMed
56.
go back to reference Fulop T Jr, Foris G, Worum I, Leovey A (1985) Age-dependent alterations of Fc gamma receptor-mediated effector functions of human polymorphonuclear leucocytes. Clin Exp Immunol 61:425PubMed Fulop T Jr, Foris G, Worum I, Leovey A (1985) Age-dependent alterations of Fc gamma receptor-mediated effector functions of human polymorphonuclear leucocytes. Clin Exp Immunol 61:425PubMed
57.
go back to reference Borrego F, Alonso MC, Galiani MD, Carracedo J, Ramirez R, Ostos B, Pena J, Solana R (1999) NK phenotypic markers and IL2 response in NK cells from elderly people. Exp Gerontol 34:253CrossRefPubMed Borrego F, Alonso MC, Galiani MD, Carracedo J, Ramirez R, Ostos B, Pena J, Solana R (1999) NK phenotypic markers and IL2 response in NK cells from elderly people. Exp Gerontol 34:253CrossRefPubMed
58.
go back to reference Kutza J, Murasko DM (1996) Age-associated decline in IL-2 and IL-12 induction of LAK cell activity of human PBMC samples. Mech Ageing Dev 90:209CrossRefPubMed Kutza J, Murasko DM (1996) Age-associated decline in IL-2 and IL-12 induction of LAK cell activity of human PBMC samples. Mech Ageing Dev 90:209CrossRefPubMed
59.
go back to reference Sansoni P, Cossarizza A, Brianti V, Fagnoni F, Snelli G, Monti D, Marcato A, Passeri G, Ortolani C, Forti E (1993) Lymphocyte subsets and natural killer cell activity in healthy old people and centenarians. Blood 82:2767PubMed Sansoni P, Cossarizza A, Brianti V, Fagnoni F, Snelli G, Monti D, Marcato A, Passeri G, Ortolani C, Forti E (1993) Lymphocyte subsets and natural killer cell activity in healthy old people and centenarians. Blood 82:2767PubMed
60.
go back to reference Rabinowich H, Goses Y, Reshef T, Klajman A (1985) Interleukin-2 production and activity in aged humans. Mech Ageing Dev 32:213CrossRefPubMed Rabinowich H, Goses Y, Reshef T, Klajman A (1985) Interleukin-2 production and activity in aged humans. Mech Ageing Dev 32:213CrossRefPubMed
61.
go back to reference Bender BS, Chrest FJ, Adler WH (1986) Phenotypic expression of natural killer cell associated membrane antigens and cytolytic function of peripheral blood cells from different aged humans. J Clin Lab Immunol 21:31PubMed Bender BS, Chrest FJ, Adler WH (1986) Phenotypic expression of natural killer cell associated membrane antigens and cytolytic function of peripheral blood cells from different aged humans. J Clin Lab Immunol 21:31PubMed
62.
go back to reference Sato T, Fuse A, Kuwata T (1979) Enhancement by IFN of natural cytotoxic ativity of lymphocytes from human cord blood and peripheral blood of aged persons. Cell Immunol 45:458PubMed Sato T, Fuse A, Kuwata T (1979) Enhancement by IFN of natural cytotoxic ativity of lymphocytes from human cord blood and peripheral blood of aged persons. Cell Immunol 45:458PubMed
63.
go back to reference Bruunsgaard H, Pedersen AN, Schroll M, Skinhoj P, Pedersen BK (2001) Decreased natural killer cell activity is associated with atherosclerosis in elderly humans. Exp Gerontol 37:127CrossRefPubMed Bruunsgaard H, Pedersen AN, Schroll M, Skinhoj P, Pedersen BK (2001) Decreased natural killer cell activity is associated with atherosclerosis in elderly humans. Exp Gerontol 37:127CrossRefPubMed
64.
go back to reference Provinciali M, Di Stefano G, Stronati S, Fabris N (1998) Generation of human lymphokine-activated killer cells following an IL-2 pulse in elderly cancer patients. Cytokine 10(2):132CrossRefPubMed Provinciali M, Di Stefano G, Stronati S, Fabris N (1998) Generation of human lymphokine-activated killer cells following an IL-2 pulse in elderly cancer patients. Cytokine 10(2):132CrossRefPubMed
65.
66.
go back to reference Bubenik J, Cinader B, Indrova M, Koh SW, Chou CT (1987) Lymphokine-activated killer (LAK) cells, I: age-dependent decline of LAK cell-mediated cytotoxicity. Immunol Lett 16:113CrossRefPubMed Bubenik J, Cinader B, Indrova M, Koh SW, Chou CT (1987) Lymphokine-activated killer (LAK) cells, I: age-dependent decline of LAK cell-mediated cytotoxicity. Immunol Lett 16:113CrossRefPubMed
67.
go back to reference Bykovskaya SN, Abronina IF, Kupriyanova TA, Bubenik J (1990) Down-regulation of LAK cell-mediated cytotoxicity: cancer and ageing. Biomed Pharmacother 44:333CrossRefPubMed Bykovskaya SN, Abronina IF, Kupriyanova TA, Bubenik J (1990) Down-regulation of LAK cell-mediated cytotoxicity: cancer and ageing. Biomed Pharmacother 44:333CrossRefPubMed
68.
go back to reference Lipschitz DA, Udupa KB, Milton KY, Thompson CO (1984) Effect of age on hematopoiesis in man. Blood 63:502PubMed Lipschitz DA, Udupa KB, Milton KY, Thompson CO (1984) Effect of age on hematopoiesis in man. Blood 63:502PubMed
69.
go back to reference Provinciali M, Di Stefano G, Fabris N (1995) Evaluation of LAK cell development in young and old healthy humans. Nat Immun 14:134PubMed Provinciali M, Di Stefano G, Fabris N (1995) Evaluation of LAK cell development in young and old healthy humans. Nat Immun 14:134PubMed
70.
go back to reference Krishnaraj R (1997) Senescence and cytokines modulate the NK cell expression. Mech Ageing Dev 96:89CrossRefPubMed Krishnaraj R (1997) Senescence and cytokines modulate the NK cell expression. Mech Ageing Dev 96:89CrossRefPubMed
71.
go back to reference Mariani E, Pulsatelli L, Meneghetti A, Dolzani P, Mazzetti I, Neri S, Ravaglia G, Forti P, Facchini A (2001) Different IL-8 production by T and NK lymphocytes in elderly subjects. Mech Ageing Dev 122:1383CrossRefPubMed Mariani E, Pulsatelli L, Meneghetti A, Dolzani P, Mazzetti I, Neri S, Ravaglia G, Forti P, Facchini A (2001) Different IL-8 production by T and NK lymphocytes in elderly subjects. Mech Ageing Dev 122:1383CrossRefPubMed
72.
go back to reference Fabris N, Provinciali M (1989) Hormones. In: Nelson D (ed) Natural immunity. Academic, New York, p 306 Fabris N, Provinciali M (1989) Hormones. In: Nelson D (ed) Natural immunity. Academic, New York, p 306
73.
go back to reference Fabris N, Mocchegiani E, Provinciali M (1997) Plasticity of neuroendocrine-thymus interactions during aging. Exp Gerontol 32:415CrossRefPubMed Fabris N, Mocchegiani E, Provinciali M (1997) Plasticity of neuroendocrine-thymus interactions during aging. Exp Gerontol 32:415CrossRefPubMed
74.
go back to reference Provinciali M, Muzzioli M, Di Stefano G, Fabris N (1991) Recovery of spleen cell natural killer activity by thyroid hormone treatment in old mice. Nat Immun Cell Growth Regul 10:22 Provinciali M, Muzzioli M, Di Stefano G, Fabris N (1991) Recovery of spleen cell natural killer activity by thyroid hormone treatment in old mice. Nat Immun Cell Growth Regul 10:22
75.
go back to reference Provinciali M, Di Stefano G, Bulian D, Stronati S, Fabris N (1997) Long-term melatonin supplementation does not recover the impairment of natural killer cell activity and lymphocyte proliferation in aging mice. Life Sci 67:857CrossRef Provinciali M, Di Stefano G, Bulian D, Stronati S, Fabris N (1997) Long-term melatonin supplementation does not recover the impairment of natural killer cell activity and lymphocyte proliferation in aging mice. Life Sci 67:857CrossRef
76.
go back to reference Provinciali M, Fabris, Pieri C (1990) Improvement of natural killer cell activity by in vitro active lipids (AL 721) administration in old mice. Mech Ageing Dev 52:245CrossRefPubMed Provinciali M, Fabris, Pieri C (1990) Improvement of natural killer cell activity by in vitro active lipids (AL 721) administration in old mice. Mech Ageing Dev 52:245CrossRefPubMed
77.
go back to reference Provinciali M, Pieri C, Fabris N (1991) Reversibility of age associated NK defect by endocrinological and/or nutritional intervention. Ann Ist Super Sanità 27:61 Provinciali M, Pieri C, Fabris N (1991) Reversibility of age associated NK defect by endocrinological and/or nutritional intervention. Ann Ist Super Sanità 27:61
78.
go back to reference Provinciali M, Di Stefano G, Bernardi A, Fabris N (1990) Role of pituitary-thyroid axis on basal and lymphokine-induced NK cell activity in ageing. Int J Neurosci 51:273PubMed Provinciali M, Di Stefano G, Bernardi A, Fabris N (1990) Role of pituitary-thyroid axis on basal and lymphokine-induced NK cell activity in ageing. Int J Neurosci 51:273PubMed
79.
go back to reference Argentati K, Bartozzi B, Bernardini G, Di Stasio G, Provinciali M (2000) Induction of NK cell activity and perforin and Granzyme B expression following continuous culture or short pulse with IL-12 in young and old mice. Eur Cytokine Netw 11:59–65PubMed Argentati K, Bartozzi B, Bernardini G, Di Stasio G, Provinciali M (2000) Induction of NK cell activity and perforin and Granzyme B expression following continuous culture or short pulse with IL-12 in young and old mice. Eur Cytokine Netw 11:59–65PubMed
80.
go back to reference Bloom ET, Kubota LF (1989) Effect of IL-2 in vitro on CTL generation in spleen cells of young and old mice: asialo GM1+ cells are required for the apparent restoration of the CTL response. Cell Immunol 119:73PubMed Bloom ET, Kubota LF (1989) Effect of IL-2 in vitro on CTL generation in spleen cells of young and old mice: asialo GM1+ cells are required for the apparent restoration of the CTL response. Cell Immunol 119:73PubMed
81.
go back to reference Kawakami K, Bloom ET (1987) Lymphokine-activated killer cells and ageing in mice: significance for defining the precursor cell. Mech Ageing Dev 41:229CrossRefPubMed Kawakami K, Bloom ET (1987) Lymphokine-activated killer cells and ageing in mice: significance for defining the precursor cell. Mech Ageing Dev 41:229CrossRefPubMed
82.
go back to reference Kawakami K, Bloom ET (1988) Lymphokine-activated killer cells derived from murine bone marrow: age-associated difference in precursor cell populations demonstrated by response to interferon. Cell Immunol 116:163PubMed Kawakami K, Bloom ET (1988) Lymphokine-activated killer cells derived from murine bone marrow: age-associated difference in precursor cell populations demonstrated by response to interferon. Cell Immunol 116:163PubMed
83.
go back to reference Saxena RK, Saxena QB, Adler W (1984) WH Interleukin-2-induced activation of natural killer activity in spleen cells from old and young mice. Immunology 51:719PubMed Saxena RK, Saxena QB, Adler W (1984) WH Interleukin-2-induced activation of natural killer activity in spleen cells from old and young mice. Immunology 51:719PubMed
84.
go back to reference Poccia F, Gougeon ML, Bonneville M, Lopez-Botet M, Moretta A, Battistini L, Wallace M, Colizzi V, Malkovsky M (1998) Innate T-cell immunity to nonpeptidic antigens. Immunol Today 19:253CrossRefPubMed Poccia F, Gougeon ML, Bonneville M, Lopez-Botet M, Moretta A, Battistini L, Wallace M, Colizzi V, Malkovsky M (1998) Innate T-cell immunity to nonpeptidic antigens. Immunol Today 19:253CrossRefPubMed
85.
go back to reference Constant P, Davodeau F, Peyrat MA, Poquet Y, Puzo G, Bonneville M, Fournie JJ (1994) Stimulation of human gamma delta T cells by nonpeptidic mycobacterial ligands. Science 264:267PubMed Constant P, Davodeau F, Peyrat MA, Poquet Y, Puzo G, Bonneville M, Fournie JJ (1994) Stimulation of human gamma delta T cells by nonpeptidic mycobacterial ligands. Science 264:267PubMed
86.
go back to reference Cipriani B, Borsellino G, Poccia F, Placido R, Tramonti D, Bach S, Battistini L, Brosnan CF (2000) Activation of C-C beta-chemokines in human peripheral blood gammadelta T cells by isopentenyl pyrophosphate and regulation by cytokines. Blood 95:39PubMed Cipriani B, Borsellino G, Poccia F, Placido R, Tramonti D, Bach S, Battistini L, Brosnan CF (2000) Activation of C-C beta-chemokines in human peripheral blood gammadelta T cells by isopentenyl pyrophosphate and regulation by cytokines. Blood 95:39PubMed
87.
go back to reference Giachino C, Granziero L, Modena V, Maiocco V, Lomater C, Fantini F, Lanzavecchia A, Migone N (1994) Clonal expansions of V delta 1+ and V delta 2+ cells increase with age and limit the repertoire of human gamma delta T cells. Eur J Immunol 24:1914PubMed Giachino C, Granziero L, Modena V, Maiocco V, Lomater C, Fantini F, Lanzavecchia A, Migone N (1994) Clonal expansions of V delta 1+ and V delta 2+ cells increase with age and limit the repertoire of human gamma delta T cells. Eur J Immunol 24:1914PubMed
88.
go back to reference Argentati K, Re F, Donnini A, Tucci MG, Franceschi C, Bartozzi B, Bernardini G, Provinciali M (2002) Numerical and functional alterations of circulating γδT lymphocytes in aged people and centenarians. J Leukoc Biol 72:65PubMed Argentati K, Re F, Donnini A, Tucci MG, Franceschi C, Bartozzi B, Bernardini G, Provinciali M (2002) Numerical and functional alterations of circulating γδT lymphocytes in aged people and centenarians. J Leukoc Biol 72:65PubMed
89.
go back to reference Colonna-Romano G, Potestio M, Aquino A, Candore G, Lio D, Caruso C (2002) Gamma/delta T lymphocytes are affected in the elderly. Exp Gerontol 37:205CrossRefPubMed Colonna-Romano G, Potestio M, Aquino A, Candore G, Lio D, Caruso C (2002) Gamma/delta T lymphocytes are affected in the elderly. Exp Gerontol 37:205CrossRefPubMed
90.
go back to reference Walker PR, Saas P, Dietrich P-Y (1997) Role of Fas Ligand (CD95L) in immune escape: the tumor cell strikes back. J Immunol 158:4521PubMed Walker PR, Saas P, Dietrich P-Y (1997) Role of Fas Ligand (CD95L) in immune escape: the tumor cell strikes back. J Immunol 158:4521PubMed
91.
go back to reference Fagnoni FF, Vescovini R, Passeri G, Bologna G, Pedrazzoni M, Lavagetto G, Casti A, Franceschi C, Passeri M, Sansoni P (2000) Shortage of circulating naive CD8+ T cells provides new insights on immunodeficiency in aging. Blood 95:2860PubMed Fagnoni FF, Vescovini R, Passeri G, Bologna G, Pedrazzoni M, Lavagetto G, Casti A, Franceschi C, Passeri M, Sansoni P (2000) Shortage of circulating naive CD8+ T cells provides new insights on immunodeficiency in aging. Blood 95:2860PubMed
92.
go back to reference Zhou D, Chrest FJ, Adler W, Munster A, Winchurch RA (1993) Increased production of TGF-beta and IL-6 by aged spleen cells. Immunol Lett 36:7CrossRefPubMed Zhou D, Chrest FJ, Adler W, Munster A, Winchurch RA (1993) Increased production of TGF-beta and IL-6 by aged spleen cells. Immunol Lett 36:7CrossRefPubMed
93.
go back to reference Goodwin JS, Messner RP (1979) Sensitivity of lymphocytes to prostaglandin E2 increases in subjects over age 70. J Clin Invest 64:434PubMed Goodwin JS, Messner RP (1979) Sensitivity of lymphocytes to prostaglandin E2 increases in subjects over age 70. J Clin Invest 64:434PubMed
94.
go back to reference Oshikawa K, Shi F, Rakhmilevich AL, Sondel PM, Mahvi DM, Yang NS (1999) Synergistic inhibition of tumor growth in a murine mammary adenocarcinoma model by combinational gene therapy using IL-12, pro-il18, and IL-1 beta converting enxyme cDNA. Proc Natl Acad Sci U S A 96:13351CrossRefPubMed Oshikawa K, Shi F, Rakhmilevich AL, Sondel PM, Mahvi DM, Yang NS (1999) Synergistic inhibition of tumor growth in a murine mammary adenocarcinoma model by combinational gene therapy using IL-12, pro-il18, and IL-1 beta converting enxyme cDNA. Proc Natl Acad Sci U S A 96:13351CrossRefPubMed
95.
go back to reference Stewart AK, Lassam NJ, Quirt IC, Bailey DJ, Rotstein LE, Krajden M, Dessureault S, Gallinger S, Cappe D, Wan Y, Addison CL, Moen RC, Gauldie J, Graham FL (1999) Adenovector-mediated gene delivery of interleukin-2 in metastatic breast cancer and melanoma: results of a phase 1 clinical trial. Gene Ther 6:350CrossRefPubMed Stewart AK, Lassam NJ, Quirt IC, Bailey DJ, Rotstein LE, Krajden M, Dessureault S, Gallinger S, Cappe D, Wan Y, Addison CL, Moen RC, Gauldie J, Graham FL (1999) Adenovector-mediated gene delivery of interleukin-2 in metastatic breast cancer and melanoma: results of a phase 1 clinical trial. Gene Ther 6:350CrossRefPubMed
96.
go back to reference Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A (1989) Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244(4905):707PubMed Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A (1989) Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244(4905):707PubMed
97.
go back to reference Berchuck A, Kamel A, Whitaker R, Kerns B, Olt G, Kinney R, Soper JT, Dodge R, Clarke-Pearson DL, Marks P (1990) Overexpression of HER-2/neu is associated with poor survival in advanced epithelial ovarian cancer. Cancer Res 50(13):4087PubMed Berchuck A, Kamel A, Whitaker R, Kerns B, Olt G, Kinney R, Soper JT, Dodge R, Clarke-Pearson DL, Marks P (1990) Overexpression of HER-2/neu is associated with poor survival in advanced epithelial ovarian cancer. Cancer Res 50(13):4087PubMed
98.
go back to reference Disis ML, Calenoff E, McLaughlin G, Murphy AE, Chen W, Groner B, Jeschke M, Lydon N, McGlynn E, Livingston RB (1994) Existent T-cell and antibody immunity to HER-2/neu protein in patients with breast cancer. Cancer Res 54(1):16PubMed Disis ML, Calenoff E, McLaughlin G, Murphy AE, Chen W, Groner B, Jeschke M, Lydon N, McGlynn E, Livingston RB (1994) Existent T-cell and antibody immunity to HER-2/neu protein in patients with breast cancer. Cancer Res 54(1):16PubMed
99.
go back to reference Disis ML, Pupa SM, Gralow JR, Dittadi R, Menard S, Cheever MA (1997) High-titer HER-2/neu protein-specific antibody can be detected in patients with early-stage breast cancer. J Clin Oncol 15(11):3363PubMed Disis ML, Pupa SM, Gralow JR, Dittadi R, Menard S, Cheever MA (1997) High-titer HER-2/neu protein-specific antibody can be detected in patients with early-stage breast cancer. J Clin Oncol 15(11):3363PubMed
100.
go back to reference Fisk B, Blevins TL, Wharton JT, Ioannides CG (1995) Identification of an immunodominant peptide of HER-2/neu protooncogene recognized by ovarian tumor-specific cytotoxic T lymphocyte lines. J Exp Med 181(6):2109CrossRefPubMed Fisk B, Blevins TL, Wharton JT, Ioannides CG (1995) Identification of an immunodominant peptide of HER-2/neu protooncogene recognized by ovarian tumor-specific cytotoxic T lymphocyte lines. J Exp Med 181(6):2109CrossRefPubMed
101.
go back to reference Peoples GE, Goedegebuure PS, Smith R, Linehan DC, Yoshino I, Eberlein TJ (1995) Breast and ovarian cancer-specific cytotoxic T lymphocytes recognize the same HER2/neu-derived peptide. Proc Natl Acad Sci U S A 92(2):432PubMed Peoples GE, Goedegebuure PS, Smith R, Linehan DC, Yoshino I, Eberlein TJ (1995) Breast and ovarian cancer-specific cytotoxic T lymphocytes recognize the same HER2/neu-derived peptide. Proc Natl Acad Sci U S A 92(2):432PubMed
102.
go back to reference Cahill DP, Kinzler KW, Vogelstein B, Lengaver C (1999) Genetic instability and Darwinian selection in tumours. Trends Cell Biol 9:M57CrossRefPubMed Cahill DP, Kinzler KW, Vogelstein B, Lengaver C (1999) Genetic instability and Darwinian selection in tumours. Trends Cell Biol 9:M57CrossRefPubMed
103.
go back to reference Colombo MP, Forni G (1994) Cytokine gene transfer in tumor inhibition and tumor therapy: where are we now? Immunol Today 15(2):48CrossRefPubMed Colombo MP, Forni G (1994) Cytokine gene transfer in tumor inhibition and tumor therapy: where are we now? Immunol Today 15(2):48CrossRefPubMed
104.
go back to reference Amici A, Smorlesi A, Noce G, Santoni G, Cappelletti P, Capparuccia L, Coppari R, Lucciarini R, Petrelli F, Provinciali M (2000) DNA vaccination with full-length or truncated Neu induced protective immunity against the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Gene Ther 7:703CrossRefPubMed Amici A, Smorlesi A, Noce G, Santoni G, Cappelletti P, Capparuccia L, Coppari R, Lucciarini R, Petrelli F, Provinciali M (2000) DNA vaccination with full-length or truncated Neu induced protective immunity against the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Gene Ther 7:703CrossRefPubMed
105.
go back to reference Pawelec G, Hirokawa K, Fulop T (2001) Altered T cell signalling in ageing. Mech Ageing Dev 122:1613CrossRefPubMed Pawelec G, Hirokawa K, Fulop T (2001) Altered T cell signalling in ageing. Mech Ageing Dev 122:1613CrossRefPubMed
106.
go back to reference Kapasi ZF, Murali-Krishna K, McRae ML, Ahmed R (2002) Defective generation but normal maintenance of memory T cells in old mice. Eur J Immunol 32:1567CrossRefPubMed Kapasi ZF, Murali-Krishna K, McRae ML, Ahmed R (2002) Defective generation but normal maintenance of memory T cells in old mice. Eur J Immunol 32:1567CrossRefPubMed
107.
go back to reference Pawelec G, Solana R, Remarque ED, Mariani E (1998) Impact of aging on innate immunity. J Leukoc Biol 64:703PubMed Pawelec G, Solana R, Remarque ED, Mariani E (1998) Impact of aging on innate immunity. J Leukoc Biol 64:703PubMed
108.
go back to reference Provinciali M, Di Stefano G, Colombo M, Della Croce F, Gandolfi MC, Daghetta L, Anichini M, Della Bitta R, Fabris N (1994) Adjuvant effect of low-dose interleukin-2 on antibody response to influenza virus vaccination in healthy elderly subjects. Mech Ageing Dev 77:75CrossRef Provinciali M, Di Stefano G, Colombo M, Della Croce F, Gandolfi MC, Daghetta L, Anichini M, Della Bitta R, Fabris N (1994) Adjuvant effect of low-dose interleukin-2 on antibody response to influenza virus vaccination in healthy elderly subjects. Mech Ageing Dev 77:75CrossRef
109.
go back to reference Provinciali M, Montenovo A, Di Stefano G, Colombo M, Daghetta L, Cairati M, Veroni C, Cassino R, Della Torre F, Fabris N (1998) Effect of zinc or zinc plus arginine supplementation on antibody titer and lymphocyte subsets after influenza virus vaccination in elderly subjects. Age Ageing 27:715PubMed Provinciali M, Montenovo A, Di Stefano G, Colombo M, Daghetta L, Cairati M, Veroni C, Cassino R, Della Torre F, Fabris N (1998) Effect of zinc or zinc plus arginine supplementation on antibody titer and lymphocyte subsets after influenza virus vaccination in elderly subjects. Age Ageing 27:715PubMed
110.
go back to reference Jackson LA, Neuzil KM, Yu O, Benson P, Barlow WE, Adams AL, Hanson CA, Mahoney LD, Shay DK, Thompson WW (2003) Effectiveness of pneumococcal polysaccharide vaccine in older adults. N Engl J Med 348:1747CrossRefPubMed Jackson LA, Neuzil KM, Yu O, Benson P, Barlow WE, Adams AL, Hanson CA, Mahoney LD, Shay DK, Thompson WW (2003) Effectiveness of pneumococcal polysaccharide vaccine in older adults. N Engl J Med 348:1747CrossRefPubMed
111.
go back to reference Steger MM, Maczek C, Berger P, Grubeck-Loebenstein B (1996b) Vaccination against tetanus in the elderly: do recommended vaccination strategies give sufficient protection? Lancet 348:762 Steger MM, Maczek C, Berger P, Grubeck-Loebenstein B (1996b) Vaccination against tetanus in the elderly: do recommended vaccination strategies give sufficient protection? Lancet 348:762
112.
go back to reference Wolters B, Junge U, Dziuba S, Roggendorf M (2003). Immunogenicity of combined hepatitis A and B vaccine in elderly persons. Vaccine 21:3623CrossRefPubMed Wolters B, Junge U, Dziuba S, Roggendorf M (2003). Immunogenicity of combined hepatitis A and B vaccine in elderly persons. Vaccine 21:3623CrossRefPubMed
113.
go back to reference Miller RA, Chrisp C (2002) T cell subset patterns that predicts resistance to spontaneous lymphoma, mammary adenocarcinoma, and fibrosarcoma in mice. J Immunol 169:1619PubMed Miller RA, Chrisp C (2002) T cell subset patterns that predicts resistance to spontaneous lymphoma, mammary adenocarcinoma, and fibrosarcoma in mice. J Immunol 169:1619PubMed
114.
go back to reference Argentati K, Re F, Serresi S, Tucci MG, Bartozzi B, Bernardini G, Provinciali M (2003) Reduced number and impaired function of circulating gammadelta T cells in patients with cutaneous primary melanoma. J Invest Dermatol 120(5):829PubMed Argentati K, Re F, Serresi S, Tucci MG, Bartozzi B, Bernardini G, Provinciali M (2003) Reduced number and impaired function of circulating gammadelta T cells in patients with cutaneous primary melanoma. J Invest Dermatol 120(5):829PubMed
115.
go back to reference Provinciali M, Smorlesi A, Donnini A, Bartozzi B, Amici A (2003) Low effectiveness of DNA vaccination against HER-2/neu in ageing. Vaccine 21(9–10):843 Provinciali M, Smorlesi A, Donnini A, Bartozzi B, Amici A (2003) Low effectiveness of DNA vaccination against HER-2/neu in ageing. Vaccine 21(9–10):843
116.
go back to reference Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Ettighausen JE, Matori YL, Skibberg JM, Shiloni E, Vetto JV, Seipp CA, Simpson C, Reichert CM (1985) Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant IL-2 to patients with metastatic cancer. N Engl J Med 313:1485PubMed Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Ettighausen JE, Matori YL, Skibberg JM, Shiloni E, Vetto JV, Seipp CA, Simpson C, Reichert CM (1985) Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant IL-2 to patients with metastatic cancer. N Engl J Med 313:1485PubMed
117.
go back to reference Rosenberg SA, Lotze MT, Yang JC, Topalian SL, Chang AE, Schwartzentruber DJ, Aebersold P, Leitman S, Linehan WM, Seipp CA, White DE, Steinberg SM (1993) Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer. J Natl Cancer Inst 85:622CrossRefPubMed Rosenberg SA, Lotze MT, Yang JC, Topalian SL, Chang AE, Schwartzentruber DJ, Aebersold P, Leitman S, Linehan WM, Seipp CA, White DE, Steinberg SM (1993) Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer. J Natl Cancer Inst 85:622CrossRefPubMed
118.
go back to reference Dussault I, Miller SC (1994). Decline in natural killer cell-mediated immunosurveillance in aging mice: a consequence of reduced cell production and tumor binding capacity. Mech Ageing Dev 75:115CrossRefPubMed Dussault I, Miller SC (1994). Decline in natural killer cell-mediated immunosurveillance in aging mice: a consequence of reduced cell production and tumor binding capacity. Mech Ageing Dev 75:115CrossRefPubMed
119.
go back to reference Negrier S, Mercatello A, Bret M, Thiesse P, Blay JY, Coronel B, Merrouche Y, Oskam R, Franks CR, Clavel Mmoskovtchenko JF, Philip T (1992) Intravenous interleukin-2 in patients over 65 with metastatic renal carcinoma. Br J Cancer 65:723PubMed Negrier S, Mercatello A, Bret M, Thiesse P, Blay JY, Coronel B, Merrouche Y, Oskam R, Franks CR, Clavel Mmoskovtchenko JF, Philip T (1992) Intravenous interleukin-2 in patients over 65 with metastatic renal carcinoma. Br J Cancer 65:723PubMed
120.
go back to reference Dussault I, Miller SC (1995) Effectiveness of immunotherapy in aged leukemic mice. Gerontology 41:204 Dussault I, Miller SC (1995) Effectiveness of immunotherapy in aged leukemic mice. Gerontology 41:204
121.
go back to reference Finn OJ (2003) Cancer vaccines: between the idea and the reality. Nat Immunol 3:630CrossRef Finn OJ (2003) Cancer vaccines: between the idea and the reality. Nat Immunol 3:630CrossRef
122.
go back to reference Ko BK, Murray JL, Disis ML, Efferson CL, Kuerer HM, Peoples GE, Ioannides CG (2003) Clinical studies of vaccines targeting breast cancer. Clin Cancer Res 9:3222PubMed Ko BK, Murray JL, Disis ML, Efferson CL, Kuerer HM, Peoples GE, Ioannides CG (2003) Clinical studies of vaccines targeting breast cancer. Clin Cancer Res 9:3222PubMed
123.
go back to reference Lollini P-L, Forni G (2003) Cancer immunoprevention: tracking down persistent tumor antigens. Trends Immunol 24:62CrossRefPubMed Lollini P-L, Forni G (2003) Cancer immunoprevention: tracking down persistent tumor antigens. Trends Immunol 24:62CrossRefPubMed
124.
go back to reference Curcio C, Di Carlo E, Clynes R, Smyth MJ, Boggio K, Quaglino E, Spadaio M, Colombo MP, Amici A, Lollini PL, Musini P, Forni G (2003) Nonredundant roles of antibody, cytokines and perforin for the immune eradication of established HER-2/neu carcinomas. J Clin Invest 111:1161CrossRefPubMed Curcio C, Di Carlo E, Clynes R, Smyth MJ, Boggio K, Quaglino E, Spadaio M, Colombo MP, Amici A, Lollini PL, Musini P, Forni G (2003) Nonredundant roles of antibody, cytokines and perforin for the immune eradication of established HER-2/neu carcinomas. J Clin Invest 111:1161CrossRefPubMed
125.
go back to reference Bernhard H, Salazar L, Schiffman K, Smorlesi A, Schmidt B, Knutson KL, Disis ML (2002) Vaccination against the HER-2/neu oncogenic protein. Endocr Relat Cancer 9:33PubMed Bernhard H, Salazar L, Schiffman K, Smorlesi A, Schmidt B, Knutson KL, Disis ML (2002) Vaccination against the HER-2/neu oncogenic protein. Endocr Relat Cancer 9:33PubMed
126.
go back to reference Tanaka Y, Koido S, Chen D, Gendler SJ, Kufe D, Gong J (2001) Vaccination with allogeneic dendritic cells fused to carcinoma cells induces antitumor immunity in MUC1 transgenic mice. Clin Immunol 101:192CrossRefPubMed Tanaka Y, Koido S, Chen D, Gendler SJ, Kufe D, Gong J (2001) Vaccination with allogeneic dendritic cells fused to carcinoma cells induces antitumor immunity in MUC1 transgenic mice. Clin Immunol 101:192CrossRefPubMed
127.
go back to reference Disis ML, Gooley TA, Rinn K, Davis D, Piepkorn M, Cheever MA, Knutson KL, Schiffman K (2002) Generation of T-cell immunity to the HER-2/neu protein after active immunization with HER-2/neu peptide-based vaccines. J Clin Oncol 20:2624CrossRefPubMed Disis ML, Gooley TA, Rinn K, Davis D, Piepkorn M, Cheever MA, Knutson KL, Schiffman K (2002) Generation of T-cell immunity to the HER-2/neu protein after active immunization with HER-2/neu peptide-based vaccines. J Clin Oncol 20:2624CrossRefPubMed
128.
go back to reference Mukherjee P, Madsen CS, Ginardi AR, Tinder TL, Jacobs F, Parker J, Agrawal B, Longenecker BM, Gendler SJ (2003) Mucin-1-specific immunotherapy in a mouse model of spontaneous breast cancer. J Immunother 26:47CrossRefPubMed Mukherjee P, Madsen CS, Ginardi AR, Tinder TL, Jacobs F, Parker J, Agrawal B, Longenecker BM, Gendler SJ (2003) Mucin-1-specific immunotherapy in a mouse model of spontaneous breast cancer. J Immunother 26:47CrossRefPubMed
129.
go back to reference Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry R, Restifo NP, Hubicki AM, Robinson MR, Raffeld M, Duray P, Seipp CA, Rogers-Freezer L, Morton KE, Mavroukakis SA, White DE, Rosenberg SA (2002) Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 298:850CrossRefPubMed Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry R, Restifo NP, Hubicki AM, Robinson MR, Raffeld M, Duray P, Seipp CA, Rogers-Freezer L, Morton KE, Mavroukakis SA, White DE, Rosenberg SA (2002) Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 298:850CrossRefPubMed
130.
go back to reference Kaesberg PR, Ershler WB (1989) The importance of immunosenescence in the incidence and malignant properties of cancer in hosts of advancer age. J Gerontol 44:63PubMed Kaesberg PR, Ershler WB (1989) The importance of immunosenescence in the incidence and malignant properties of cancer in hosts of advancer age. J Gerontol 44:63PubMed
131.
go back to reference Seymour K, Pettit S, O’Flaherty E, Charnley RM, Kirby JA (1999) Selection of metastatic tumor phenotypes by host immune systems. Lancet 354:1989CrossRefPubMed Seymour K, Pettit S, O’Flaherty E, Charnley RM, Kirby JA (1999) Selection of metastatic tumor phenotypes by host immune systems. Lancet 354:1989CrossRefPubMed
132.
go back to reference Kreisle RA, Stebler BA, Ershler WB (1990) Effect of host age on tumor-associated angiogenesis in mice. J Natl Cancer Inst 82:44PubMed Kreisle RA, Stebler BA, Ershler WB (1990) Effect of host age on tumor-associated angiogenesis in mice. J Natl Cancer Inst 82:44PubMed
133.
go back to reference Pili R, Guo Y, Chang J, Nakanishi H, Martin GR, Passaniti A (1994) Altered angiogenesis underlying age-dependent changes in tumor growth. J Natl Cancer Inst 86:1303PubMed Pili R, Guo Y, Chang J, Nakanishi H, Martin GR, Passaniti A (1994) Altered angiogenesis underlying age-dependent changes in tumor growth. J Natl Cancer Inst 86:1303PubMed
134.
go back to reference Onozuka S, Tawara I, Shimizu J, Sakaguchi S, Fujita T, Nakayama E (1999) Tumor rejection by in vivo administration of anti-CD25 monoclonal antibody. Cancer Res 59:3128PubMed Onozuka S, Tawara I, Shimizu J, Sakaguchi S, Fujita T, Nakayama E (1999) Tumor rejection by in vivo administration of anti-CD25 monoclonal antibody. Cancer Res 59:3128PubMed
135.
go back to reference Jones E, Dahm-Vicker M, Simon AK, Green A, Powrie F, Cerundolo V, Gallimore A (2002) Depletion of CD25+ regulatory cells results in suppression of melanoma growth and induction of autoreactivity in mice. Cancer Immunity 2:1PubMed Jones E, Dahm-Vicker M, Simon AK, Green A, Powrie F, Cerundolo V, Gallimore A (2002) Depletion of CD25+ regulatory cells results in suppression of melanoma growth and induction of autoreactivity in mice. Cancer Immunity 2:1PubMed
136.
go back to reference Murakami M, Sakamoto A, Bender J, Kappler J, Marrack P (2002) CD25+CD4+ T cells contribute to the control of memory CD8+ T cells. Proc Natl Acad Sci U S A 99:8832CrossRefPubMed Murakami M, Sakamoto A, Bender J, Kappler J, Marrack P (2002) CD25+CD4+ T cells contribute to the control of memory CD8+ T cells. Proc Natl Acad Sci U S A 99:8832CrossRefPubMed
Metadata
Title
Immunoprevention and immunotherapy of cancer in ageing
Authors
Mauro Provinciali
Arianna Smorlesi
Publication date
01-02-2005
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 2/2005
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-004-0539-3

Other articles of this Issue 2/2005

Cancer Immunology, Immunotherapy 2/2005 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine