Paradoxical roles of the immune system during cancer development

Nature Reviews Cancer

Volumn 6, Issue 1, 2006, Pages 24-37

  De Visser, Karin E ^a   Eichten, Alexandra ^b   Coussens, Lisa M ^b,c,d  

^a NETHERLANDS CANCER INSTITUTE   (Netherlands)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOGENESIS; BREAST CANCER; CANCER INCIDENCE; CARCINOGENESIS; CELL PROLIFERATION; HEART GRAFT; IMMUNE SYSTEM; IMMUNOCOMPETENT CELL; IMMUNOMODULATION; KAPOSI SARCOMA; KIDNEY GRAFT; LEUKOCYTE; LIVER GRAFT; NONHODGKIN LYMPHOMA; NONHUMAN; OVARY CANCER; PRIORITY JOURNAL; PROSTATE CANCER; REVIEW; SKIN CANCER; UROGENITAL TRACT CANCER; UTERINE CERVIX CANCER; UTERUS CANCER;

ANIMALS; DISEASE MODELS, ANIMAL; HUMANS; IMMUNE SYSTEM; IMMUNITY, ACTIVE; IMMUNITY, NATURAL; INFLAMMATION; LEUKOCYTES; MICE; NEOPLASMS;

EID: 30144443269     PISSN: 1474175X     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrc1782     Document Type: Review

References (107)

1. Hamerman, J. A., Ogasawara, K. & Lanier, L. L. NK cells in innate immunity. Curr. Opin. Immunol. 17, 29-35 (2005).
2. Degli-Esposti, M. A. & Smyth, M. J. Close encounters of different kinds: dendritic cells and NK cells take centre stage. Nature Rev. Immunol. 5, 112-124 (2005).
3. Raulet, D. H. Interplay of natural killer cells and their receptors with the adaptive immune response. Nature. Immunol. 5, 1038-1114 (2004). References 1-3 are comprehensive reviews on the role of dendritic and natural killer cells during tumour development.
4. Finch, C. E. & Crimmins, E. M. Inflammatory exposure and historical changes in human life-spans. Science 305, 1736-1739 (2004). A thoughtful analysis of historical changes in human exposure to inflammatory agents that are correlated with cancer incidence and lifespan.
5. Balkwill, F. & Mantovani, A. Inflammation and cancer: back to Virchow? Lancet 357, 539-545 (2001).
6. Coca, S. et al. The prognostic significance of intratumoral natural killer cells in patients with colorectal carcinoma. Cancer 79, 2320-2328 (1997).
7. Ishigami, S. et al. Prognostic value of intratumoral natural killer cells in gastric carcinoma. Cancer 88, 577-583 (2000).
8. Ribatti, D. et al. Tumor vascularity and tryptase-positive mast cells correlate with a poor prognosis in melanoma. Eur. J. Clin. Invest. 33, 420-425 (2003).
9. Imada, A., Shijubo, N., Kojima, H. & Abe, S. Mast cells correlate with angiogenesis and poor outcome in stage I lung adenocarcinoma. Eur. Respir. J. 15, 1087-1093 (2000).
10. Leek, R. D. et al. Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res. 56, 4625-4629 (1996).
11. Leek, R. D., Landers, R. J., Harris, A. L. & Lewis, C. E. Necrosis correlates with high vascular density and focal macrophage infiltration in invasive carcinoma of the breast. Br. J. Cancer 79, 991-995 (1999).
12. Balkwill, F., Charles, K. A. & Mantovani, A. Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 7, 211-217 (2005). A timely and detailed review of clinical and experimental literature that discusses paracrine communication networks between immune cells and cells at risk for cancer development.
13. Pagano, J. S. et al. Infectious agents and cancer: criteria for a causal relation. Semin. Cancer Biol. 14, 453-471 (2004).
14. Velicer, C. M. et al. Antibiotic use in relation to the risk of breast cancer. JAMA 291, 827-835 (2004).
15. Enzler, T. et al. Deficiencies of GM-CSF and interferon γlink inflammation and cancer. J. Exp. Med. 197, 1213-1219 (2003). A detailed analysis of immune-competent mice that are deficient for GMCSF and IFNγ, which demonstrates that failure to normalize tissue homeostasis and clear low-level microbial infections results in chronic inflammation that underlies an increased incidence of haematologic and solid-tissue cancers.
16. Korzenik, J. R., Dieckgraefe, B. K., Valentine, J. F., Hausman, D. F. & Gilbert, M. J. Sargramostim for active Crohn's disease. N. Engl. J. Med. 352, 2193-2201 (2005).
17. Dannenberg, A. & Subbaramaiah. Targeting cyclooxygenase-2 in human neoplasia: rationale and promise. Cancer Cell 4, 431-436 (2003).
18. Zou, W. Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nature Rev. Cancer 5, 263-274 (2005). An excellent review that provides an extensive overview of immunosuppressive networks in the microenvironment of developing tumours.
19. Finke, J., Ferrone, S., Frey, A., Mufson, A. & Ochoa, A. Where have all the T cells gone? Mechanisms of immune evasion by tumors. Immunol. Today 20, 158-160 (1999).
20. Curiel, T. J. et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nature Med. 10, 942-94 (2004).
21. Serafini, P. et al. Derangement of immune responses by myeloid suppressor cells. Cancer Immunol. Immunother. 53, 64-72 (2004).
22. Coussens, L. M., Hanahan, D. & Arbeit, J. M. Genetic predisposition and parameters of malignant progression in K14-HPV16 transgenic mice. Am. J. Pathol. 149, 1899-1917 (1996).
23. Arbeit, J., Howley, P. & Hanahan, D. Chronic estrogen-induced cervical and vaginal squamous carcinogenesis in HPV16 transgenic mice. Proc. Natl Acad. Sci. USA 93, 2930-2935 (1996).
24. Smith-McCune, K., Zhu, Y. H., Hanahan, D. & Arbeit, J. Cross-species comparison of angiogenesis during the premalignant stages of squamous carcinogenesis in the human cervix and K14-HPV16 transgenic mice. Cancer Res. 57, 1294-1300 (1997).
25. van Kempen, L. C. L. et al. Epithelial carcinogenesis: dynamic interplay between neoplastic cells and their microenvironment. Differentiation 70, 501-623 (2002).
26. Giraudo, E., Inoue, M. & Hanahan, D. An aminobisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis. J. Clin. Invest. 114, 623-633 (2004).
27. Coussens, L. M. et al. Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis. Genes Dev. 13, 1382-1397 (1999).
28. de Visser, K. E., Korets, L. V. & Coussens, L. M. De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent. Cancer Cell 7, 411-423 (2005). A study from the authors' laboratory that reports that inflammation-associated cancer development in skin-cancer-prone transgenic mice is dependent upon serum factors that are derived from activated peripheral B lymphocytes, so revealing the complexity of interactions between innate and adaptive immune cells that regulate epithelial cancer development.
29. Lin, E. Y., Nguyen, A. V., Russell, R. G. & Pollard, J. W. Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J. Exp. Med. 193, 727-740 (2001). Using the well-characterized MMTV-PyMT model of mammary carcinogenesis, the authors rendered mice CSF1-deficient to block macrophage recruitment into neoplastic tissue and therefore demonstrated that macrophages deliver permissive factors necessary for development of late-stage carcinomas and pulmonary metastases.
30. Pollard, J. W. Tumour-educated macrophages promote tumour progression and metastasis. Nature Rev. Cancer 4, 71-78 (2004). A detailed review on the role of macrophages during mammary carcinogenesis.
31. Sparmann, A. & Bar-Sagi, D. Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis. Cancer Cell 6, 447-458 (2004).
32. Smyth, M. J., Crowe, N. Y. & Godfrey, D. I. NK cells and NKT cells collaborate in host protection from methylcholanthrene-induced fibrosarcoma. Int. Immunol. 13, 459-463 (2001).
33. Hayakawa, Y. et al. IFN-γ-mediated inhibition of tumor angiogenesis by natural killer T-cell ligand, α-galactosylceramide. Blood 100, 1728-1733 (2002).
34. Esposito, I. et al. Inflammatory cells contribute to the generation of an angiogenic phenotype in pancreatic ductal adenocarcinoma. J. Clin. Pathol. 57, 630-636 (2004).
35. Yano, H. et al. Mast cell infiltration around gastric cancer cells correlates with tumor angiogenesis and metastasis. Gastric Cancer 2, 26-32 (1999).
36. Egeblad, M. & Werb, Z. New functions for the matrix metalloproteinases in cancer progression. Nature Rev. Cancer 2, 161-174 (2002).
37. Coussens, L. M., Tinkle, C. L., Hanahan, D. & Werb, Z. MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell 103, 481-490 (2000).
38. Huang, S. et al. Contributions of stromal metalloproteinase-9 to angiogenesis and growth of human ovarian carcinoma in mice. J. Natl Cancer Inst. 94, 1134-1142 (2002).
39. Hiratsuka, S. et al. MMP9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis. Cancer Cell 2, 289-300 (2002).
40. Bergers, G. et al. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nature Cell Biol. 2, 737-744 (2000).
41. Overall, C. M., McQuibban, G. A. & Clark-Lewis, I. Discovery of chemokine substrates for matrix metalloproteinases by exosite scanning: a new tool for degradomics. Biol. Chem. 383, 1059-1066 (2002).
42. Lynch, C. C. et al. MMP-7 promotes prostate cancer-induced osteolysis via the solubilization of RANKL. Cancer Cell 7, 485-496 (2005). A provocative study that reveals a previously unknown role for MMP7/matrilysin as a crucial regulator of osteolysis during prostate-cancer bone metastases by virtue of its ability to regulate bioavailability of RANKL.
43. Coleman, R. E. Bisphosphonates in breast cancer. Ann. Oncol. 16, 687-695 (2005).
44. Psaty, B. M. & Furberg, C. D. COX-2 inhibitors - lessons in drug safety. N. Engl. J. Med. 352, 1133-1135 (2005).
45. Liu, C. H. et al. Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice. J. Biol. Chem. 276, 18563-18569 (2001).
46. Jacoby, R. F., Seibert, K., Cole, C. E., Kelloff, G. & Lubet, R. A. The cyclooxygenase-2 inhibitor celecoxib is a potent preventive and therapeutic agent in the min mouse model of adenomatous polyposis. Cancer Res. 60, 5040-5044 (2000).
47. Δ716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 87, 803-809 (1996).
48. Zha, S., Yegnasubramanian, V., Nelson, W. G., Isaacs, W. B. & De Marzo, A. M. Cyclooxygenases in cancer: progress and perspective. Cancer Lett. 215, 1-20 (2004).
49. Basu, G. D. et al. Cyclooxygenase-2 inhibitor induces apoptosis in breast cancer cells in an in vivo model of spontaneous metastatic breast cancer. Mol. Cancer Res. 2,632-642 (2004).
50. Chang, S. H., Ai, Y., Breyer, R. M., Lane, T. F. & Hla, T. The prostaglandin E2 receptor EP2 is required for cyclooxygenase 2-mediated mammary hyperplasia. Cancer Res. 65, 4496-4499 (2005).
51. Barbera-Guillem, E., Nyhus, J. K., Wolford, C. C., Friece, C. R. & Sampsel, J. W. Vascular endothelial growth factor secretion by tumor-infiltrating macrophages essentially supports tumor angiogenesis, and IgG immune complexes potentiate the process. Cancer Res. 62, 7042-7049 (2002).
52. Szlosarek, P. W. & Balkwill, F. R. Tumour necrosis factor α: a potential target for the therapy of solid tumours. Lancet Oncol. 4, 565-573 (2003).
53. Madhusudan, S. et al. A phase II study of etanercept (Enbrel), a tumor necrosis factor α inhibitor in patients with metastatic breast cancer. Clin. Cancer Res. 10, 6528-6534 (2004).
54. Pikarsky, E. et al. NF-κB functions as a tumour promoter in inflammation-associated cancer. Nature 431, 461-466 (2004).
55. Greten, F. R. et al. IKKβ links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118, 285-296 (2004). These two elegant studies use state-of-the-art conditional-knockout mice in combination with different chemical carcinogenesis strategies to cause inflammation-induced hepatocellular carcinoma or colitis-associated cancer, thereby demonstrating that inactivation of NFκB signalling in cells at risk for malignant conversion or in infiltrating inflammatory cells results in attenuated cancer formation. This highlights the necessity of paracrine interactions for cancer development.
56. + myeloid cells. J. Immunol. 166, 5398-5406 (2001).
57. + T cells: a common basis between tumor immunity and autoimmunity. J. Immunol. 163, 5211-5218 (1999).
58. Onizuka, S. et al. Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor α) monoclonal antibody. Cancer Res. 59, 3128-3133 (1999).
59. Seitz, C. S., Lin, Q., Deng, H. & Khavari, P. A. Alterations in NF-κB function in transgenic epithelial tissue demonstrate a growth inhibitory role for NF-κB. Proc. Natl Acad. Sci. USA 95, 2307-2312 (1998).
60. Dajee, M. et al. NF-κB blockade and oncogenic Ras trigger invasive human epidermal neoplasia. Nature 421, 639-643 (2003).
61. Scott, K. A. et al. An anti-tumor necrosis factor-α antibody inhibits the development of experimental skin tumors. Mol. Cancer Ther. 2, 445-451 (2003).
62. Wang, C. Y., Cusack, J. C. Jr, Liu, R. & Baldwin, A. S. Jr. Control of inducible chemoresistance: enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-κB. Nature Med. 5, 412-417 (1999).
63. Lenz, H. J. Clinical update: proteasome inhibitors in solid tumors. Cancer Treat. Rev. 29, 41-48 (2003).
64. Boshoff, C. & Weiss, R. AIDS-related malignancies. Nature Rev. Cancer 2, 373-382 (2002).
65. Clifford, G. M. et al. Cancer risk in the Swiss HIV Cohort Study: associations with immunodeficiency, smoking, and highly active antiretroviral therapy. J. Natl Cancer Inst. 97, 425-432 (2005).
66. Herrero, J. I. et al. De novo neoplasia after liver transplantation: an analysis of risk factors and influence on survival. Liver Transpl. 11, 89-97 (2005).
67. Fung, J. J. et al. De novo malignancies after liver transplantation: a major cause of late death. Liver Transpl. 7, S109-S118 (2001).
68. Rosenberg, S. A., Yang, J. C. & Restifo, N. P. Cancer immunotherapy: moving beyond current vaccines. Nature Med. 10, 909-915 (2004). A thoughtful assessment of current anticancer immunotherapeutical approaches and critical analysis of successes and failures with current strategies.
69. + T cell tolerance and cancer immunotherapy. J. Immunother. 26, 1-11 (2003).
70. Overwijk, W. W. Breaking tolerance in cancer immunotherapy: time to ACT. Curr. Opin. Immunol. 17, 187-194 (2005).
71. + T cells. J. Exp. Med. 197, 1017-1028 (2003).
72. + T Cell-mediated antigen-specific immunotherapy in a mouse model of cervical cancer. Cancer Res. 65, 2018-2025 (2005).
73. Girardi, M. et al. Regulation of cutaneous malignancy by γδ T cells. Science 294, 605-609 (2001). This study highlights a dual role for adaptive immunity during chemically induced skin carcinogenesis and reveals that the absence of γδ T cells results in increased susceptibility to MCA-and DMBA/TPA-induced carcinomas, whereas the absence of αβ T cells only increases suceptibility to MCA-induced carcinomas, and reduces susceptibility to DMBA/TPA-induced carcinomas.
74. Smyth, M. J. & Godfrey, D. I. NKT cells and tumor immunity - a double-edged sword. Nature Immunol. 1, 459-460 (2000).
75. Papamichail, M., Perez, S. A., Gritzapis, A. D. & Baxevanis, C. N. Natural killer lymphocytes: biology, development, and function. Cancer Immunol. Immunother. 53, 176-186 (2004).
76. Terabe, M. et al. NKT cell-mediated repression of tumor immunosurveillance by IL-13 and the IL-4R-STAT6 pathway. Nature Immunol. 1, 515-520 (2000).
77. Moodycliffe, A. M., Nghiem, D., Clydesdale, G. & Ullrich, S. E. Immune suppression and skin cancer development: regulation by NKT cells. Nature Immunol. 1, 521-525 (2000).
78. Hoebe, K., Janssen, E. & Beutler, B. The interface between innate and adaptive immunity. Nature Immunol. 5, 971-974 (2004). An excellent review of the complexities of interactions that regulate efficient and appropriate adaptive and innate immune-cell interactions.
79. Firestein, G. S. Evolving concepts of rheumatoid arthritis. Nature 423, 356-361 (2003).
80. Gorman, C., Leandro, M. & Isenberg, D. B cell depletion in autoimmune disease. Arthritis Res. Ther. 5, 17-21 (2003).
81. Randolph, G. J., Angeli, V. & Swartz, M. A. Dendritic-cell trafficking to lymph nodes through lymphatic vessels. Nature Rev. Immunol. 5, 617-628 (2005).
82. Snell, G. D. Incompatibility reactions to tumor homotransplants with particular reference to the role of the tumor: a review. Cancer Res. 17, 2-10 (1957).
83. Kaliss, N. Immunological enhancement of tumor homografts in mice: a review. Cancer Res. 18, 992-1003 (1958).
84. Ran, M. & Witz, I. P. Tumor-associated immunoglobulins. Enhancement of syngeneic tumors by IgG2-containing tumor eluates. Int. J. Cancer 9, 242-247 (1972).
85. Agassy-Cahalon, L., Yaakubowicz, M., Witz, I. P. & Smorodinsky, N. I. The immune system during the precancer period: naturally-occurring tumor reactive monoclonal antibodies and urethane carcinogenesis. Immunol. Lett. 18, 181-189 (1988).
86. Brodt, P. & Gordon, J. Natural resistance mechanisms may play a role in protection against chemical carcinogenesis. Cancer Immunol. Immunother. 13, 125-127 (1982).
87. + and B lymphocytes in transplantation immunity. II. Augmented rejection of tumor allografts by mice lacking B cells. Transplantation 55, 1356-1361 (1993).
88. Ibanez, O. M. et al. Low antibody responsiveness is found to be associated with resistance to chemical skin tumorigenesis in several lines of Biozzi mice. Cancer Lett. 136, 153-158 (1999).
89. Siegel, C. T. et al. Enhanced growth of primary tumors in cancer-prone mice after immunization against the mutant region of an inherited oncoprotein. J. Exp. Med. 191, 1945-1956 (2000). Using classical immunological approaches, this is a clear study reporting that active immunization can result in enhancement of chemically induced tumors, which correlates with induction of humoral immune responses in experimental mouse models. This indicates that immunotherapeutical approaches must consider the duality of immunomodulation therapies.
90. Barbera-Guillem, E., May, K. F. Jr, Nyhus, J. K. & Nelson, M. B. Promotion of tumor invasion by cooperation of granulocytes and macrophages activated by anti-tumor antibodies. Neoplasia 1, 453-460 (1999).
91. Tomer, Y., Sherer, Y. & Shoenfeld, Y. Autoantibodies, autoimmunity and cancer. Oncol. Rep. 5, 753-761 (1998).
92. Tan, E. M. & Shi, F. D. Relative paradigms between autoantibodies in lupus and autoantibodies in cancer. Clin. Exp. Immunol. 134, 169-177 (2003).
93. Edwards, J. C. et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N. Engl. J. Med. 350, 2572-2581 (2004).
94. Oligino, T. J. & Dalrymple, S. A. Targeting B cells for the treatment of rheumatoid arthritis. Arthritis Res. Ther. 5, 7-11 (2003).
95. Coussens, L. M., Fingleton, B. & Matrisian, L. M. Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science 295, 2387-2392 (2002).
96. Whitcomb, D. C. Inflammation and cancer V. Chronic pancreatitis and pancreatic cancer. Am. J. Physiol. Gastrointest. Liver Physiol. 287, G315-G319 (2004).
97. De Luca, A. & Iaquinto, G. Helicobacter pylori and gastric diseases: a dangerous association. Cancer Lett. 213, 1-10 (2004).
98. Brechot, C. Pathogenesis of hepatitis B virus-related hepatocellular carcinoma: old and new paradigms. Gastroenterology 127, 56-61 (2004).
99. Parsonnet, J. Molecular mechanisms for inflammation-promoted pathogenesis of cancer - The Sixteenth International Symposium of the Sapporo Cancer Seminar. Cancer Res. 57, 3620-3624 (1997).
100. Schmielau, J. & Finn, O. J. Activated granulocytes and granulocyte-derived hydrogen peroxide are the underlying mechanism of suppression of T-cell function in advanced cancer patients. Cancer Res. 61, 4756-4760 (2001).
101. Stuart, L. M. & Ezekowitz, R. A. Phagocytosis: elegant complexity. Immunity 22, 539-550 (2005).
102. Gallagher, B., Wang, Z., Schymura, M. J., Kahn, A. & Fordyce, E. J. Cancer incidence in New York State acquired immunodeficiency syndrome patients. Am. J. Epidemiol. 154, 544-556 (2001).
103. Biggar, R. J., Kirby, K. A., Atkinson, J., McNeel, T. S. & Engels, E. Cancer risk in elderly persons with HIV/AIDS. J. Acquir. Immune Defic. Syndr. 36, 861-868 (2004).
104. Frisch, M., Biggar, R. J., Engels, E. A. & Goedert, J. J. Association of cancer with AIDS-related immunosuppression in adults. JAMA 285, 1736-1745 (2001).
105. Haagsma, E. B. et al. Increased cancer risk after liver transplantation: a population-based study. J. Hepatol. 34, 84-91 (2001).
106. Engels, E. A. & Goedert, J. J. Human immunodeficiency virus/acquired immunodeficiency syndrome and cancer: past, present, and future. J. Natl Cancer Inst. 97, 407-409 (2005).
107. Stewart, T., Tsai, S. C., Grayson, H., Henderson, R. & Opelz, G. Incidence of de-novo breast cancer in women chronically immunosuppressed after organ transplantation. Lancet 346, 796-798 (1995).