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01-11-2005 | Novel Therapeutic Strategies

Strategies of Tumor Immune Evasion

Author: Professor Dr Barbara Seliger

Published in: BioDrugs | Issue 6/2005

Abstract

During the last decade, increased understanding of the molecular mechanisms responsible for immune activation to protect against challenges by tumor cells has revolutionized the field of immunotherapy research. It has been demonstrated that the dysfunction of the host’s immune system represents one of the major mechanisms by which tumors evade immunosurveillance. This is due, for example, to T cell anergy, the existence of regulatory T cells, and systemic defects of dendritic cells derived from tumor patients. In addition, escape from immunosurveillance can also be linked to tumor-related factors, including secretion of immunosuppressive cytokines, resistance to apoptosis, and deficient expression of immunomodulatory molecules and major histocompatibility complex (MHC) class I antigens possibly due to immunoselection. Both host- and tumor-related mechanisms can lead to a failure to mount a proper anti-tumor-specific immune response, and these are frequently key factors in limiting the success of cancer immunotherapy.

Ossendorp F, Toes RE, Offringa R, et al. Importance of CD4(+) T helper cell responses in tumor immunity. Immunol Lett 2000; 74: 75–9PubMedCrossRef

Schuler G, Schuler-Thurner B, Steinman RM. The use of dendritic cells in cancer immunotherapy. Curr Opin Immunol 2003 Apr; 15(2): 138–47PubMedCrossRef

Dunn GP, Bruce AT, Ikeda H, et al. Cancer immunoediting: from immunosurveil-lance to tumor escape. Nat Immunol 2002 Nov; 3(11): 991–8PubMedCrossRef

Mapara MY, Sykes M. Tolerance and cancer: mechanisms of tumor evasion and strategies for breaking tolerance. J Clin Oncol 2004; 22: 1136–51PubMedCrossRef

Mahnke YD, Speiser D, Luescher IF, et al. Recent advances in tumour antigen-specific therapy: in vivo veritas. Int J Cancer 2005 Jan 10; 113(2): 173–8PubMedCrossRef

Rosenberg SA. A new era for cancer immunotherapy based on the genes that encode cancer antigens. Immunity 1999 Mar; 10(3): 281–7PubMedCrossRef

Gilboa E. The makings of a tumor rejection antigen. Immunity 1999 Sep; 11(3): 263–70PubMedCrossRef

Wang RF. The role of MHC class II-restricted tumor antigens and CD+ T cells in antitumor immunity. Trends Immunol 2001; 22: 269–76PubMedCrossRef

Houghton AN, Gold JS, Blachere NE. Immunity against cancer: lessons learned from melanoma. Curr Opin Immunol 2001 Apr; 13(2): 134–40PubMedCrossRef

10.

Sahin U, Tureci O, Pfreundschuh M. Serological identification of human tumor antigens. Curr Opin Immunol 1997 Oct; 9(5): 709–16PubMedCrossRef

11.

Schoenberger SP, Toes RE, van der Voort EI, et al. T-cell help for cytotoxic T lymphocytes is mediated by CD40-DC40L interactions. Nature 1998 Jun 4; 393(6684): 480–3PubMedCrossRef

12.

De Smedt T, Smith J, Baum P, et al. OX40 costimulation enhances the development of T cell responses induced by dendritic cells in vivo. J Immunol 2002 Jan 15; 168(2): 661–70PubMed

13.

Djeu JY, Jiang K, Wei S. A view to a kill: signals triggering cytotoxicity. Clin Cancer Res 2002 Mar; 8(3): 636–40PubMed

14.

Raja SM, Metkar SS, Froelich CJ. Cytotoxic granule-mediated apoptosis: unraveling the complex mechanism. Curr Opin Immunol 2003 Oct; 15(5): 528–32PubMedCrossRef

15.

Rosenberg SA, Yang JC, Schwartzentruber DJ, et al. Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nat Med 1998 Mar; 4(3): 321–7PubMedCrossRef

16.

Eaton JD, Perry MJ, Nicholson S, et al. Allogeneic whole-cell vaccine: a phase I/II study in men with hormone-refractory prostate cancer. BJU Int 2002 Jan; 89(1): 19–26PubMedCrossRef

17.

Malmberg KJ. Effective immunotherapy against cancer. Cancer Immunol Immunother 2004 Oct; 53(10): 879–92PubMedCrossRef

18.

Timmerman JM, Singh G, Hermanson G, et al. Immunogenicity of a plasmid DNA vaccine encoding chimeric idiotype in patients with B-cell lymphoma. Cancer Res 2002 Oct 15; 62(20): 5845–52PubMed

19.

Toes RE, Hoeben RC, van der Voort EI, et al. Protective anti-tumor immunity induced by vaccination with recombinant adenoviruses encoding multiple tumor-associated cytotoxic T lymphocyte epitopes in a string-of-beads fashion. Proc Natl Acad Sci U S A 1997 Dec 23; 94(26): 14660–5PubMedCrossRef

20.

Chen DS, Davis MM. Cellular immunotherapy: antigen recognition is just the beginning. Springer Semin Immunopathol 2005 Jun; 27(1): 119–27PubMedCrossRef

21.

Surman DR, Dudley ME, Overwijk WW, et al. Cutting edge: CD4+ T cell control of CD8+ T cell reactivity to a model tumor antigen. J Immunol 2000; 164: 562–5PubMed

22.

Slingluff Jr CL, Petroni GR, Yamshchikov GV, et al. Clinical and immunologie results of a randomized phase II trial of vaccination using four melanoma peptides either administered in granulocyte-macrophage colony-stimulating factor in adjuvant or pulsed on dendritic cells. J Clin Oncol 2003; 21: 4016–26PubMedCrossRef

23.

McNeel DG, Knutson KL, Schiffman K, et al. Pilot study of an HLA-A2 peptide vaccine using flt3 ligand as a systemic vaccine adjuvant. J Clin Immunol 2003; 23: 62–72PubMedCrossRef

24.

Leitner WW, Hwang LN, de Veer MJ, et al. Alphavirus-based DNA vaccine breaks immunological tolerance by activating innate antiviral pathways. Nat Med 2003 Jan; 9(1): 33–9PubMedCrossRef

25.

Marchand M, Punt CJ, Aamdal S, et al. Immunisation of metastatic cancer patients with MAGE-3 protein combined with adjuvant SBAS-2: a clinical report. Eur J Cancer 2003; 39: 70–7PubMedCrossRef

26.

Schuler-Thurner B, Schultz ES, Berger TG, et al. Rapid induction of tumor-specific type 1 T helper cells in metastatic melanoma patients by vaccination with mature, cryopreserved, peptide-loaded monocyte-derived dendritic cells. J Exp Med 2002; 195: 1279–88PubMedCrossRef

27.

Rosenberg SA, Dudley ME. Cancer regression in patients with metastatic melanoma after the transfer of autologous antitumor lymphocytes. Proc Natl Acad Sci U S A 2004 Oct 5; 101Suppl. 2: 14639–45PubMedCrossRef

28.

Dudley ME, Wunderlich JR, Robbins PF, et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 2002 Oct 25; 298(5594: 850–4PubMedCrossRef

29.

Yee C, Thompson JA, Byrd D, et al. Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T cells. Proc Natl Acad Sci U S A 2002; 99: 16168–73PubMedCrossRef

30.

Ayyoub M, Zippelius A, Pittet MJ, et al. Activation of human melanoma reactive CD8+ T cells by vaccination with an immunogenic peptide analog derived from Melan-A/melanoma antigen recognized by T cells-1. Clin Cancer Res 2003; 9: 669–77PubMed

31.

Valmori D, Dutoit V, Ayyoub M, et al. Simultaneous CD8+ T cell responses to multiple tumor antigen epitopes in a multipeptide melanoma vaccine. Cancer Immun 2003 Oct 28; 3: 15PubMed

32.

Chen JL, Stewart-Jones G, Bossi G, et al. Structural and kinetic basis for heightened immunogenicity of T cell vaccines. J Exp Med 2005; 201: 1243–55PubMedCrossRef

33.

Martin-Fontecha A, Sebastiani S, Hopken UE, et al. Regulation of dendritic cell migration to the draining lymph node: impact on T lymphocyte traffic and priming. J Exp Med 2003; 198: 615–21PubMedCrossRef

34.

Kammertoens T, Schüler T, Blankenstein T. Immunotherapy: target the stroma to hit the tumor. Trends Mol Med 2005 May; 11(5): 225–31PubMedCrossRef

35.

Harrop R, Ryan MG, Golding H, et al. Monitoring of human immunological responses to vaccinia virus. Methods Mol Biol 2004; 269: 243–66PubMed

36.

Reddy M, Eirikis E, Davis C, et al. Comparative analysis of lymphocyte marker expression and cytokine secretion profile in stimulated human peripheral blood mononuclear cell cultures: an in vitro model to monitor cellular immune function. J Immunol Methods 2004 Oct; 293(1–2): 127–42PubMedCrossRef

37.

Sheehy ME, McDermott AB, Furlan SN, et al. A novel technique for the fluorometric assessment of T lymphocyte antigen specific lysis. J Immunol Methods 2001; 249: 99–110PubMedCrossRef

38.

Speiser DE, Pittet MJ, Rimoldi D, et al. Evaluation of melanoma vaccines with molecularly defined antigens by ex vivo monitoring of tumor-specific T cells. Semin Cancer Biol 2003 Dec; 13(6): 461–72PubMedCrossRef

39.

Schmittel A, Keilholz U, Thiel E, et al. Quantification of tumor-specific T lymphocytes with the ELISPOT assay. J Immunother 2000 May–Jun; 23(3): 289–95PubMedCrossRef

40.

Gabrilovich D. Mechanisms and functional significance of tumour-induced dendritic-cell defects. Nat Rev Immunol 2004; 4: 941–52PubMedCrossRef

41.

Coulie PG, Connerotte T. Human tumor-specific T lymphocytes: does function matter more than number? Curr Opin Immunol 2005 Jun; 17(3): 320–5PubMedCrossRef

42.

Lurquin C, Lethé B, De Plaen E, et al. Contrasting frequencies of anti-tumor and anti-vaccine T cells in metastases of a melanoma patient vaccinated with a MAGE tumor antigen. J Exp Med 2005 Jan 17; 201(2): 249–57PubMedCrossRef

43.

Lonchay C, van der Bruggen P, Connerotte T, et al. Correlation between tumor regression and T cell responses in melanoma patients vaccinated with a MAGE antigen. Proc Natl Acad Sci U S A 2004 Oct 5; 101 Suppl. 2: 14631–8CrossRef

44.

Marincola FM, Wang E, Herlyn M, et al. Tumors as elusive targets of T cell based active immunotherapy. Trends Immunol 2003 Jun; 24(6): 335–42PubMedCrossRef

45.

Seliger B, Maeurer MJ, Ferrone S. Antigen-processing machinery breakdown and tumor growth. Immunol Today 2000 Sep; 21(9): 455–64PubMedCrossRef

46.

Restifo NP. Not so Fas: re-evaluating the mechanisms of immune privilege and tumor escape. Nat Med 2000 May; 6(5): 493–5PubMedCrossRef

47.

Favre-Felix N, Fromentin A, Hammann A, et al. Cutting edge: the tumor counterattack hypothesis revisited: colon cancer cells do not induce T cell apoptosis via the Fas (CD95, APO-1) pathway. J Immunol 2000 May 15; 164(10): 5023–7PubMed

48.

Hersey P, Zhang XD. How melanoma cells evade trail-induced apoptosis. Nat Rev Cancer 2001 Nov; 1(2): 142–50PubMedCrossRef

49.

Algarra I, Garcia-Lora A, Cabrera T, et al. The selection of tumor variants with altered expression of classical and non-classical MHC class I molecules: implications for tumor immune escape. Cancer Immunol Immunother 2004 Oct; 53(10): 904–10PubMedCrossRef

50.

Garcia-Lora A, Martinez M, Algarra I, et al. MHC class I-deficient metastatic tumor variants immunoselected by T lymphocytes originate from the coordinated downregulation of AMP components. Int J Cancer 2003 Sep 10; 106(4): 521–7PubMedCrossRef

51.

Chen HL, Gabrilovich D, Tampe R, et al. A functionally defective allele of TAP1 results in loss of MHC class I antigen presentation in a human lung cancer. Nat Genet 1996 Jun; 13(2): 210–3PubMedCrossRef

52.

Seliger B, Ritz U, Abele R, et al. Immune escape of melanoma: first evidence of structural alterations in two distinct components of the MCH class I antigen processing pathway. Cancer Res 2001 Dec 15; 61(24): 8647–50PubMed

53.

Hodson I, Bock M, Ritz U, et al. Analysis of the structural integrity of the TAP2 gene in renal cell carcinoma. Int J Oncol 2003 Oct; 23(4): 991–9PubMed

54.

Hicklin DJ, Dellaratta DV, Kishore R, et al. Beta2-microglobulin gene mutations in human melanoma cells: molecular characterization and implications for immune surveillance. Melanoma Res 1997 Aug; 7 Suppl. 2: S67–74

55.

Ibrahim EC, Guerra N, Lacombe MJ, et al. Tumor-specific up-regulation of the non-classical class I HLA-G antigen expression in renal carcinoma. Cancer Res 2001 Sep 15; 61(18): 6838–45PubMed

56.

Paul P, Cabestre FA, Le Gal FA, et al. Heterogeneity of HLA-G gene transcription and protein expression in malignant melanoma biopsies. Cancer Res 1999 Apr 15; 59(8): 1954–60PubMed

57.

Groh V, Wu J, Yee C, et al. Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature 2002 Oct 17; 419(6908): 734–8PubMedCrossRef

58.

Sotomayor EM, Borrello I, Tubb E, et al. Conversion of tumor-specific CD4+ T-cell tolerance to T-cell priming through in vivo ligation of CD40. Nat Med 1999 Jul; 5(7): 780–7PubMedCrossRef

59.

Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 2002 Aug; 8(8): 793–800PubMed

60.

Kawakami Y, Okada T, Akada M. Development of immunotherapy for pancreatic cancer. Pancreas 2004 Apr; 28(3): 320–5PubMedCrossRef

61.

Chen Q, Daniel V, Maher DW, et al. Production of IL-10 by melanoma cells: examination of its role in immunosuppression mediated by melanoma. Int J Cancer 1994 Mar 1; 56(5): 755–60PubMedCrossRef

62.

Tada T, Ohzeki S, Utsumi K, et al. Transforming growth factor-beta-induced inhibition of T cell function: susceptibility difference in T cells of various phenotypes and functions and its relevance to immunosuppression in the tumor-bearing state. J Immunol 1991 Feb 1; 146(3): 1077–82PubMed

63.

Gorelik L, Flavell RA. Immune-mediated eradication of tumors through the blockade of transforming growth factor-beta signaling in T cells. Nat Med 2001 Oct; 7(10): 1118–22PubMedCrossRef

64.

Zeidler R, Eissner G, Meissner P, et al. Downregulation of TAPI in B lymphocytes by cellular and Epstein-Barr virus-encoded interleukin-10. Blood 1997 Sep 15; 90(6): 2390–7PubMed

65.

Strand S, Hofmann WJ, Hug H, et al. Lymphocyte apoptosis induced by CD95 (APO-1/Fas) ligand-expressing tumor cells-a mechanism of immune evasion? Nat Med 1996 Dec; 2(12): 1361–6PubMedCrossRef

66.

Pitti RM, Marsters SA, Lawrence DA, et al. Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Nature 1998 Dec 17; 396(6712): 699–703PubMedCrossRef

67.

Kiessling R, Wasserman K, Horiguchi S, et al. Tumor-induced immune dysfunction. Cancer Immunol Immunother 1999 Oct; 48(7): 353–62PubMedCrossRef

68.

Surh CD, Sprent J. T-cell apoptosis detected in situ during positive and negative selection in the thymus. Nature 1994; 372: 100–3PubMedCrossRef

69.

Ramsdell F, Fowlkes BJ. Clonal deletion versus clonal anergy: the role in thymus in inducing self tolerance. Science 1990; 248: 1342–8PubMedCrossRef

70.

Aoe T, Okamoto Y, Saito T. Activated macrophages induce structural abnormalities of the T cell receptor-CD3 complex. J Exp Med 1995 May 1; 181(5): 1881–6PubMedCrossRef

71.

Kono K, Ressing ME, Brandt RM, et al. Decreased expression of signal-transducing zeta chain in peripheral T cells and natural killer cells in patients with cervical cancer. Clin Cancer Res 1996 Nov; 2(11): 1825–8PubMed

72.

Mizoguchi H, O’Shea JJ, Longo DL, et al. Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice. Science 1992 Dec 11; 258(5089): 1795–8PubMedCrossRef

73.

Finke JH, Zea AH, Stanley J, et al. Loss of T-cell receptor zeta chain and p561ck in T-cells infiltrating human renal cell carcinoma. Cancer Res 1993 Dec 1; 53(23): 5613–6PubMed

74.

Whiteside TL. Down-regulation of zeta-chain expression in T cells: a biomarker of prognosis in cancer? Cancer Immunol Immunother 2004 Oct; 53(10): 865–78PubMedCrossRef

75.

Sakaguchi S, Sakaguchi N, Shimizu J, et al. Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol Rev 2001 Aug; 182: 18–32PubMedCrossRef

76.

Jonuleit H, Schmitt E. The regulatory T cell family: distinct subsets and their interrelations. J Immunol 2003 Dec 15; 171(12): 6323–7PubMed

77.

Woo EY, Chu CS, Goletz TJ, et al. Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer Res 2001 Jun 15; 61(12): 4766–72PubMed

78.

Steinman RM, Nussenzweig MC. Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc Natl Acad Sci U S A 2002 Jan 8; 99(1): 351–8PubMedCrossRef

79.

Albert ML, Jegathesan M, Darnell RB. Dendritic cell maturation is required for the cross-tolerization of CD8+ T cells. Nat Immunol 2001 Nov; 2(11): 1010–7PubMedCrossRef

80.

Hoffmann TK, Muller-Berghaus J, Ferris RL, et al. Alterations in the frequency of dendritic cell subsets in the peripheral circulation of patients with squamous cell carcinomas of the head and neck [published erratum appears in Clin Cancer Res 2003 Jan; 9 (1): 441]. Clin Cancer Res 2002 Jun; 8(6): 1787–93PubMed

81.

Kusmartsev S, Gabrilovich DI. Immature myeloid cells and cancer-associated immune suppression. Cancer Immunol Immunother 2002; 51: 293–8PubMedCrossRef

82.

Delia Bella S, Gennaro M, Vaccari M, et al. Altered maturation of peripheral blood dendritic cells in patients with breast cancer. Br J Cancer 2003 Oct 20; 89(8): 1463–72PubMedCrossRef

83.

Gabrilovich DI, Ishida T, Nadaf S, et al. Antibodies to vascular endothelial growth factor enhance the efficacy of cancer immunotherapy by improving endogenous dendritic cell function. Clin Cancer Res 1999 Oct; 5(10): 2963–70PubMed

84.

Hoentjen F, Sartor RB, Ozaki M, et al. STAT3 regulates NF-kappaB recruitment to the IL-12p40 promoter in dendritic cells. Blood 2005 Jan 15; 105(2): 689PubMedCrossRef

85.

Nefedova Y, Huang M, Kusmartsev S, et al. Hyperactivation of STAT3 is involved in abnormal differentiation of dendritic cells in cancer. J Immunol 2004 Jan 1; 172(1): 464–74PubMed

86.

Arista MC, Callopoli A, De Franceschi L, et al. Flow cytometric study of lymphocyte subsets in patients at different stages of colorectal carcinoma. Dis Colon Rectum 1994 Feb; 37(2 Suppl.): 30–4CrossRef

87.

Knabel M, Franz TJ, Schiemann M, et al. Reversible MHC multimer staining for functional isolation of T-cell populations and effective adoptive transfer. Nat Med 2002; 8: 631–7PubMedCrossRef

88.

Whelan JA, Dunbar PR, Price DA, et al. Specificity of CTL interactions with peptide-MHC class I tetrameric complexes is temperature dependent. J Immunol 1999 Oct 15; 163(8): 4342–8PubMed

89.

Palmowski M, Salio M, Dunbar RP, et al. The use of HLA class I tetramers to design a vaccination strategy for melanoma patients. Immunol Rev 2002 Oct; 188(1): 155–63PubMedCrossRef

90.

Pittet MJ, Rubio-Godoy V, Bioley G, et al. Alpha 3 domain mutants of peptide/ MHC class I multimers allow the selective isolation of high avidity tumor-reactive CD8 T cells. J Immunol 2003 Aug 15; 171(4): 1844–9PubMed

91.

Reichstetter S, Ettinger RA, Liu AW, et al. Distinct T cell interactions with HLA class II tetramers characterize a spectrum of TCR affinities in the human antigen-specific T cell response. J Immunol 2000; 165: 6994–8PubMed

92.

Skinner PJ, Daniels MA, Schmidt CS, et al. Cutting edge: in situ tetramer staining of antigen-specific T cells in tissues. J Immunol 2000; 165: 613–7PubMed

93.

Kienzle N, Olver S, Buttigieg K, et al. The fluorolysis assay, a highly sensitive method for measuring the cytolytic activity of T cells at very low numbers. J Immunol Methods 2002; 267: 99–108PubMedCrossRef

94.

Rice AM, Jones KL, Hart DN. DC preparations for therapy. Cytotherapy 2004; 6(2): 99–104PubMedCrossRef

95.

Lechmann M, Berchtold S, Hauber J, et al. CD83 on dendritic cells: more than just a marker for maturation. Trends Immunol 2002 Jun; 23(6): 273–5PubMedCrossRef

96.

Wang E, Phan GQ, Marincola FM. T-cell-directed cancer vaccines: the melanoma model. Expert Opin Biol Ther 2001 Mar; 1(2): 277–90PubMedCrossRef

97.

Soen Y, Chen DS, Stuge T, et al. A novel cellular microarray identifies functional deficiencies in tumor-specific T cell responses. J Clin Oncol 2003; 22: 2510

98.

Morse MA, Chui S, Hobeika A, et al. Recent developments in therapeutic cancer vaccines. Nat Clin Pract Oncol 2005 Feb; 2(2): 108–13PubMedCrossRef

99.

Antonia S, Mulé JJ, Weber JS. Current developments of immunotherapy in the clinic. Curr Opin Immunol 2004 Apr; 16(2): 130–6PubMedCrossRef

100.

Acres B, Paul S, Haegel-Kronenberger H, et al. Therapeutic cancer vaccines. Curr Opin Mol Ther 2004 Feb; 6(1): 40–7PubMed

101.

Knutson KL, Disis ML. Tumor antigen-specific T helper cells in cancer immunity and immunotherapy. Cancer Immunol Immunother 2005 Aug; 54(8): 721–8PubMedCrossRef

102.

Korman A, Yellin M, Keler T. Tumor immunotherapy: preclinical and clinical activity of anti-CTLA4 antibodies. Curr Opin Investig Drugs 2005 Jun; 6(6): 582–91PubMed

103.

Overwijk WW. Breaking tolerance in cancer immunotherapy: time to ACT. Curr Opin Immunol 2005 Apr; 17(2): 187–94PubMedCrossRef

104.

Klebanoff CA, Khong HAT, Antony PA, et al. Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy. Trends Immunol 2005 Feb; 26(2): 111–7PubMedCrossRef

105.

Kipriyanov SM, Le Gall F. Recent advances in the generation of bispecific antibodies for tumor immunotherapy. Curr Opin Drug Discov Devel 2004 Mar; 7(2): 233–42PubMed

Title: Strategies of Tumor Immune Evasion
Author: Professor Dr Barbara Seliger
Publication date: 01-11-2005
Publisher: Springer International Publishing
Published in: BioDrugs / Issue 6/2005
Print ISSN: 1173-8804
Electronic ISSN: 1179-190X
DOI: https://doi.org/10.2165/00063030-200519060-00002

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Strategies of Tumor Immune Evasion

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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