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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 10/2008

01-10-2008 | Symposium Paper

Spontaneous immune responses to sporadic tumors: tumor-promoting, tumor-protective or both?

Author: Karin E. de Visser

Published in: Cancer Immunology, Immunotherapy | Issue 10/2008

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Abstract

Cancer cells cannot develop into invasive cancers without interactions with cells and soluble mediators present in the tumor microenvironment. Accumulating evidence indicates that the immune system is a critical determinant of malignant outgrowth; however, the tumor-modulating effects of spontaneous immune responses towards nascent malignancies are rather paradoxical. Both cancer-protective and cancer-promoting features of the immune system have been described. This review will discuss the role of the dynamic inflammatory tumor microenvironment during cancer development and progression, and will focus on the intriguing question: “Do malignancies develop in spite of—or because of—spontaneous immune responses?” Special emphasis will be put on recent progress in our understanding of the immune system’s double-edged sword function during de novo carcinogenesis.
Literature
1.
Balkwill F, Charles KA, Mantovani A (2005) Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 7:211–217PubMedCrossRef
2.
3.
Blankenstein T (2007) Do autochthonous tumors interfere with effector T cell responses? Semin Cancer Biol 17:267–274PubMedCrossRef
4.
5.
Buckanovich RJ, Facciabene A, Kim S, Benencia F, Sasaroli D, Balint K, Katsaros D, O’Brien-Jenkins A, Gimotty PA, Coukos G (2008) Endothelin B receptor mediates the endothelial barrier to T cell homing to tumors and disables immune therapy. Nat Med 14:28–36PubMedCrossRef
6.
Burnet FM (1970) The concept of immunological surveillance. Prog Exp Tumor Res 13:1–27PubMed
7.
Casanovas O, Hicklin DJ, Bergers G, Hanahan D (2005) Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell 8:299–309PubMedCrossRef
8.
Coussens LM, Raymond WW, Bergers G, Laig-Webster M, Behrendtsen O, Werb Z, Caughey GH, Hanahan D (1999) Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis. Genes Dev 13:1382–1397PubMedCrossRef
9.
Coussens LM, Tinkle CL, Hanahan D, Werb Z (2000) MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell 103:481–490PubMedCrossRef
10.
Croci DO, Zacarias Fluck MF, Rico MJ, Matar P, Rabinovich GA, Scharovsky OG (2007) Dynamic cross-talk between tumor and immune cells in orchestrating the immunosuppressive network at the tumor microenvironment. Cancer Immunol Immunother 56:1687–1700PubMedCrossRef
11.
Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, Zhu Y, Wei S, Kryczek I, Daniel B, Gordon A, Myers L, Lackner A, Disis ML, Knutson KL, Chen L, Zou W (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10:942–949PubMedCrossRef
12.
de Visser KE, Coussens LM (2006) The inflammatory tumor microenvironment and its impact on cancer development. Contrib Microbiol 13:118–137PubMedCrossRef
13.
de Visser KE, Eichten A, Coussens LM (2006) Paradoxical roles of the immune system during cancer development. Nat Rev Cancer 6:24–37PubMedCrossRef
14.
de Visser KE, Korets LV, Coussens LM (2005) De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent. Cancer Cell 7:411–423PubMedCrossRef
15.
de Visser KE, Korets LV, Coussens LM (2004) Early neoplastic progression is complement independent. Neoplasia 6:768–776PubMedCrossRef
16.
Derksen PW, Liu X, Saridin F, van der Gulden H, Zevenhoven J, Evers B, van Beijnum JR, Griffioen AW, Vink J, Krimpenfort P, Peterse JL, Cardiff RD, Berns A, Jonkers J (2006) Somatic inactivation of E-cadherin and p53 in mice leads to metastatic lobular mammary carcinoma through induction of anoikis resistance and angiogenesis. Cancer Cell 10:437–449PubMedCrossRef
17.
Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD (2002) Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 3:991–998PubMedCrossRef
18.
Dunn GP, Koebel CM, Schreiber RD (2006) Interferons, immunity and cancer immunoediting. Nat Rev Immunol 6:836–848PubMedCrossRef
19.
Dunn GP, Old LJ, Schreiber RD (2004) The immunobiology of cancer immunosurveillance and immunoediting. Immunity 21:137–148PubMedCrossRef
20.
Engel AM, Svane IM, Rygaard J, Werdelin O (1997) MCA sarcomas induced in scid mice are more immunogenic than MCA sarcomas induced in congenic, immunocompetent mice. Scand J Immunol 45:463–470PubMedCrossRef
21.
Engle SJ, Ormsby I, Pawlowski S, Boivin GP, Croft J, Balish E, Doetschman T (2002) Elimination of colon cancer in germ-free transforming growth factor beta 1-deficient mice. Cancer Res 62:6362–6366PubMed
22.
Enzler T, Gillessen S, Manis JP, Ferguson D, Fleming J, Alt FW, Mihm M, Dranoff G (2003) Deficiencies of GM-CSF and interferon gamma link inflammation and cancer. J Exp Med 197:1213–1219PubMedCrossRef
23.
Fischer C, Jonckx B, Mazzone M, Zacchigna S, Loges S, Pattarini L, Chorianopoulos E, Liesenborghs L, Koch M, De Mol M, Autiero M, Wyns S, Plaisance S, Moons L, van Rooijen N, Giacca M, Stassen JM, Dewerchin M, Collen D, Carmeliet P (2007) Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels. Cell 131:463–475PubMedCrossRef
24.
Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoue F, Bruneval P, Cugnenc PH, Trajanoski Z, Fridman WH, Pages F (2006) Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313:1960–1964PubMedCrossRef
25.
Garbe AI, Vermeer B, Gamrekelashvili J, von Wasielewski R, Greten FR, Westendorf AM, Buer J, Schmid RM, Manns MP, Korangy F, Greten TF (2006) Genetically induced pancreatic adenocarcinoma is highly immunogenic and causes spontaneous tumor-specific immune responses. Cancer Res 66:508–516PubMedCrossRef
26.
Girardi M, Oppenheim DE, Steele CR, Lewis JM, Glusac E, Filler R, Hobby P, Sutton B, Tigelaar RE, Hayday AC (2001) Regulation of cutaneous malignancy by gammadelta T cells. Science 294:605–609PubMedCrossRef
27.
Greten FR, Eckmann L, Greten TF, Park JM, Li ZW, Egan LJ, Kagnoff MF, Karin M (2004) IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118:285–296PubMedCrossRef
28.
Guerra C, Schuhmacher AJ, Canamero M, Grippo PJ, Verdaguer L, Perez-Gallego L, Dubus P, Sandgren EP, Barbacid M (2007) Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell 11:291–302PubMedCrossRef
29.
Gupta RA, Dubois RN (2001) Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer 1:11–21PubMedCrossRef
30.
Khong HT, Restifo NP (2002) Natural selection of tumor variants in the generation of “tumor escape” phenotypes. Nat Immunol 3:999–1005PubMedCrossRef
31.
Koebel CM, Vermi W, Swann JB, Zerafa N, Rodig SJ, Old LJ, Smyth MJ, Schreiber RD (2007) Adaptive immunity maintains occult cancer in an equilibrium state. Nature 450:903–907PubMedCrossRef
32.
Kusmartsev S, Gabrilovich DI (2006) Role of immature myeloid cells in mechanisms of immune evasion in cancer. Cancer Immunol Immunother 55:237–245PubMedCrossRef
33.
Lin EY, Nguyen AV, Russell RG, Pollard JW (2001) Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med 193:727–740PubMedCrossRef
34.
Moore RJ, Owens DM, Stamp G, Arnott C, Burke F, East N, Holdsworth H, Turner L, Rollins B, Pasparakis M, Kollias G, Balkwill F (1999) Mice deficient in tumor necrosis factor-alpha are resistant to skin carcinogenesis. Nat Med 5:828–831PubMedCrossRef
35.
Ochsenbein AF, Klenerman P, Karrer U, Ludewig B, Pericin M, Hengartner H, Zinkernagel RM (1999) Immune surveillance against a solid tumor fails because of immunological ignorance. Proc Natl Acad Sci USA 96:2233–2238PubMedCrossRef
36.
Ohshima H (2003) Genetic and epigenetic damage induced by reactive nitrogen species implications in carcinogenesis. Toxicol Lett 140–141:99–104PubMedCrossRef
37.
Parish CR (2003) Cancer immunotherapy: the past, the present and the future. Immunol Cell Biol 81:106–113PubMedCrossRef
38.
Pikarsky E, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S, Gutkovich-Pyest E, Urieli-Shoval S, Galun E, Ben-Neriah Y (2004) NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature 431:461–466PubMedCrossRef
39.
40.
Serafini P, De Santo C, Marigo I, Cingarlini S, Dolcetti L, Gallina G, Zanovello P, Bronte V (2004) Derangement of immune responses by myeloid suppressor cells. Cancer Immunol Immunother 53:64–72PubMedCrossRef
41.
Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ, Schreiber RD (2001) IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410:1107–1111PubMedCrossRef
42.
Siegel CT, Schreiber K, Meredith SC, Beck-Engeser GB, Lancki DW, Lazarski CA, Fu YX, Rowley DA, Schreiber H (2000) Enhanced growth of primary tumors in cancer-prone mice after immunization against the mutant region of an inherited oncoprotein. J Exp Med 191:1945–1956PubMedCrossRef
43.
Soucek L, Lawlor ER, Soto D, Shchors K, Swigart LB, Evan GI (2007) Mast cells are required for angiogenesis and macroscopic expansion of Myc-induced pancreatic islet tumors. Nat Med 13:1211–1218PubMedCrossRef
44.
Stutman O (1974) Tumor development after 3-methylcholanthrene in immunologically deficient athymic-nude mice. Science 183:534–536PubMedCrossRef
45.
Tan TT, Coussens LM (2007) Humoral immunity, inflammation and cancer. Curr Opin Immunol 19:209–216PubMedCrossRef
46.
van den Broek ME, Kagi D, Ossendorp F, Toes R, Vamvakas S, Lutz WK, Melief CJ, Zinkernagel RM, Hengartner H (1996) Decreased tumor surveillance in perforin-deficient mice. J Exp Med 184:1781–1790CrossRef
47.
Willimsky G, Blankenstein T (2005) Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance. Nature 437:141–146PubMedCrossRef
48.
Wyckoff J, Wang W, Lin EY, Wang Y, Pixley F, Stanley ER, Graf T, Pollard JW, Segall J, Condeelis J (2004) A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res 64:7022–7029PubMedCrossRef
49.
Yu P, Rowley DA, Fu YX, Schreiber H (2006) The role of stroma in immune recognition and destruction of well-established solid tumors. Curr Opin Immunol 18:226–231PubMedCrossRef
50.
Zou W (2005) Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer 5:263–274PubMedCrossRef
Metadata
Title
Spontaneous immune responses to sporadic tumors: tumor-promoting, tumor-protective or both?
Author
Karin E. de Visser
Publication date
01-10-2008
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 10/2008
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-008-0501-x

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