Abstract
Tumor-associated inflammation is a frequently observed phenomenon considered to be one of the major hallmarks of neoplastic disease progression. Recent data show that inflammatory processes around malignancies are able to both support and suppress neoplastic progression depending on the phase of tumor progression or the cytokine context of ongoing immunological processes in the tumor microenvironment. Recent concepts of malignancy-associated inflammation and its impact on dendritic cell functions suggest that the net effect of inflammation on the balance between tumor growth and dendritic cell-controlled immunity is continuously changing over time, as inflammatory signals are frequently re-interpreted along with cancer progression. Initially, inflammation sustains malignant conversion and supports survival of tumor cells in cryptic cancers; however, it also allows their recognition by dendritic cells via damage-associated molecular patterns. In progressing cancers, inflammation contributes to malignant invasion, angiogenesis, and metastasis formation. In addition, via suppressing dendritic cell activation, maturation, and disrupting communication between dendritic cells and NK or T cells, it also corrupts antitumor immune responses launched by both the innate and adaptive immune systems. On the other hand, upon appropriate stimulation of specific toll-like receptors, tumor-infiltrating myeloid and plasmacytoid dendritic cells can be successfully activated, leading to harsh inflammatory reactions ultimately resulting in rapid rejection of tumor cells. Thus, ubiquitous presence of inflammation around tumors can be exploited not only for early detection of cryptic malignant lesions but also for inducing dendritic cell-mediated rejection of established malignancies.
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References
Aggarwal, B. B., Shishodia, S., Sandur, S. K., Pandey, M. K. and Sethi, G. 2006. Inflammation and cancer: how hot is the link? Biochem Pharmacol 72:1605–1621.
Arina, A., Murillo, O., Dubrot, J., Azpilikueta, A., Alfaro, C., Perez-Gracia, J. L., Bendandi, M., Palencia, B., Hervas-Stubbs, S. and Melero, I. 2007. Cellular liaisons of natural killer lymphocytes in immunology and immunotherapy of cancer. Expert Opin Biol Ther 7:599–615.
Arnott, C. H., Scott, K. A., Moore, R. J., Hewer, A., Phillips, D. H., Parker, P., Balkwill, F. R. and Owens, D. M. 2002. Tumour necrosis factor-alpha mediates tumour promotion via a PKC alpha- and AP-1-dependent pathway. Oncogene 21:4728–4738.
Balkwill, F. and Mantovani, A. 2001. Inflammation and cancer: back to Virchow? Lancet 357:539–545.
Ben-Baruch, A. 2006. Inflammation-associated immune suppression in cancer: the roles played by cytokines, chemokines and additional mediators. Semin Cancer Biol 16:38–52.
Bui, J. D. and Schreiber, R. D. 2007. Cancer immunosurveillance, immunoediting and inflammation: independent or interdependent processes? Curr Opin Immunol 19:203–208.
Carneiro, L. A., Magalhaes, J. G., Tattoli, I., Philpott, D. J. and Travassos, L. H. 2008. Nod-like proteins in inflammation and disease. J Pathol 214:136–148.
Chen, R., Alvero, A. B., Silasi, D. A., Steffensen, K. D. and Mor, G. 2008. Cancers take their Toll--the function and regulation of Toll-like receptors in cancer cells. Oncogene 27:225–233.
Chomarat, P., Banchereau, J., Davoust, J. and Palucka, A. K. 2000. IL-6 switches the differentiation of monocytes from dendritic cells to macrophages. Nat Immunol 1:510–514.
Cools, N., Ponsaerts, P., Van Tendeloo, V. F. and Berneman, Z. N. 2007. Regulatory T cells and human disease. Clin Dev Immunol 2007:89195.
Coussens, L. M. and Werb, Z. 2002. Inflammation and cancer. Nature 420:860–867.
DeNardo, D. G., Johansson, M. and Coussens, L. M. 2008. Immune cells as mediators of solid tumor metastasis. Cancer Metastasis Rev 27:11–18.
Dhodapkar, M. V., Dhodapkar, K. M. and Palucka, A. K. 2008. Interactions of tumor cells with dendritic cells: balancing immunity and tolerance. Cell Death Differ 15:39–50.
Diegelmann, R. F. and Evans, M. C. 2004. Wound healing: an overview of acute, fibrotic and delayed healing. Front Biosci 9:283–289.
Dunn, G. P., Bruce, A. T., Ikeda, H., Old, L. J. and Schreiber, R. D. 2002. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 3:991–998.
Dunn, G. P., Old, L. J. and Schreiber, R. D. 2004. The immunobiology of cancer immunosurveillance and immunoediting. Immunity 21:137–148.
Fallarino, F., Grohmann, U., Hwang, K. W., Orabona, C., Vacca, C., Bianchi, R., Belladonna, M. L., Fioretti, M. C., Alegre, M. L. and Puccetti, P. 2003. Modulation of tryptophan catabolism by regulatory T cells. Nat Immunol 4:1206–1212.
Gorski, K. S., Waller, E. L., Bjornton-Severson, J., Hanten, J. A., Riter, C. L., Kieper, W. C., Gorden, K. B., Miller, J. S., Vasilakos, J. P., Tomai, M. A. and Alkan, S. S. 2006. Distinct indirect pathways govern human NK-cell activation by TLR-7 and TLR-8 agonists. Int Immunol 18:1115–1126.
Grulich, A. E., van Leeuwen, M. T., Falster, M. O. and Vajdic, C. M. 2007. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet 370:59–67.
Hudson, J. D., Shoaibi, M. A., Maestro, R., Carnero, A., Hannon, G. J. and Beach, D. H. 1999. A proinflammatory cytokine inhibits p53 tumor suppressor activity. J Exp Med 190:1375–1382.
Karin, M. 2006. Nuclear factor-kappaB in cancer development and progression. Nature 441:431–436.
Kedrin, D., van Rheenen, J., Hernandez, L., Condeelis, J. and Segall, J. E. 2007. Cell motility and cytoskeletal regulation in invasion and metastasis. J Mammary Gland Biol Neoplasia 12:143–152.
Kijima, M., Yamaguchi, T., Ishifune, C., Maekawa, Y., Koyanagi, A., Yagita, H., Chiba, S., Kishihara, K., Shimada, M. and Yasutomo, K. 2008. Dendritic cell-mediated NK cell activation is controlled by Jagged2-Notch interaction. Proc Natl Acad Sci USA 105:7010–7015.
Koebel, C. M., Vermi, W., Swann, J. B., Zerafa, N., Rodig, S. J., Old, L. J., Smyth, M. J. and Schreiber, R. D. 2007. Adaptive immunity maintains occult cancer in an equilibrium state. Nature 450:903–907.
Kroczek, R. A., Mages, H. W. and Hutloff, A. 2004. Emerging paradigms of T-cell co-stimulation. Curr Opin Immunol 16:321–327.
Li, M. O., Wan, Y. Y., Sanjabi, S., Robertson, A. K. and Flavell, R. A. 2006. Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol 24:99–146.
Lucas, M., Schachterle, W., Oberle, K., Aichele, P. and Diefenbach, A. 2007. Dendritic cells prime natural killer cells by trans-presenting interleukin 15. Immunity 26:503–517.
Maeda, H. and Akaike, T. 1998. Nitric oxide and oxygen radicals in infection, inflammation, and cancer. Biochemistry (Mosc) 63:854–865.
Mager, D. L. 2006. Bacteria and cancer: cause, coincidence or cure? A review. J Transl Med 4:14.
Mantovani, A., Romero, P., Palucka, A. K. and Marincola, F. M. 2008. Tumour immunity: effector response to tumour and role of the microenvironment. Lancet 371:771–783.
Marelli-Berg, F. M., Okkenhaug, K. and Mirenda, V. 2007. A two-signal model for T cell trafficking. Trends Immunol 28:267–273.
Marincola, F. M., Wang, E., Herlyn, M., Seliger, B. and Ferrone, S. 2003. Tumors as elusive targets of T-cell-based active immunotherapy. Trends Immunol 24:335–342.
Martinez, F. O., Sica, A., Mantovani, A. and Locati, M. 2008. Macrophage activation and polarization. Front Biosci 13:453–461.
Mocellin, S., Mandruzzato, S., Bronte, V. and Marincola, F. M. 2004. Cancer vaccines: pessimism in check. Nat Med 10:1278–1279 (author reply 1279–1280).
Monsurro, V., Wang, E., Yamano, Y., Migueles, S. A., Panelli, M. C., Smith, K., Nagorsen, D., Connors, M., Jacobson, S. and Marincola, F. M. 2004. Quiescent phenotype of tumor-specific CD8+ T cells following immunization. Blood 104:1970–1978.
Moore, K. W., O'Garra, A., de Waal Malefyt, R., Vieira, P. and Mosmann, T. R. 1993. Interleukin-10. Annu Rev Immunol 11:165–190.
Muruve, D. A., Petrilli, V., Zaiss, A. K., White, L. R., Clark, S. A., Ross, P. J., Parks, R. J. and 1Tschopp, J. 2008. The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response. Nature 452:103–107.
Panelli, M. C., Stashower, M. E., Slade, H. B., Smith, K., Norwood, C., Abati, A., Fetsch, P., Filie, A., Walters, S. A., Astry, C., Arico, E., Zhao, Y., Selleri, S., Wang, E. and Marincola, F. M. 2007. Sequential gene profiling of basal cell carcinomas treated with imiquimod in a placebo-controlled study defines the requirements for tissue rejection. Genome Biol 8:R8.
Papadavid, E., Stratigos, A. J. and Falagas, M. E. 2007. Imiquimod: an immune response modifier in the treatment of precancerous skin lesions and skin cancer. Expert Opin Pharmacother 8:1743–1755.
Pawelec, G. 2004. Tumour escape: antitumour effectors too much of a good thing? Cancer Immunol Immunother 53:262–274.
Rock, K. L. and Kono, H. 2008. The inflammatory response to cell death. Annu Rev Pathol 3:99–126.
Rosenberg, S. A., Restifo, N. P., Yang, J. C., Morgan, R. A. and Dudley, M. E. 2008. Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer 8:299–308.
Rosenberg, S. A., Yang, J. C. and Restifo, N. P. 2004. Cancer immunotherapy: moving beyond current vaccines. Nat Med 10:909–915.
Sauter, B., Albert, M. L., Francisco, L., Larsson, M., Somersan, S. and Bhardwaj, N. 2000. Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J Exp Med 191:423–434.
Schiller, M., Metze, D., Luger, T. A., Grabbe, S. and Gunzer, M. 2006. Immune response modifiers--mode of action. Exp Dermatol 15:331–341.
Schon, M. P. and Schon, M. 2008. TLR7 and TLR8 as targets in cancer therapy. Oncogene 27:190–199.
Shankaran, V., Ikeda, H., Bruce, A. T., White, J. M., Swanson, P. E., Old, L. J. and Schreiber, R. D. 2001. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410:1107–1111.
Shanker, A., Verdeil, G., Buferne, M., Inderberg-Suso, E. M., Puthier, D., Joly, F., Nguyen, C., Leserman, L., Auphan-Anezin, N. and Schmitt-Verhulst, A. M. 2007. CD8 T cell help for innate antitumor immunity. J Immunol 179:6651–6662.
Sica, A., Schioppa, T., Mantovani, A. and Allavena, P. 2006. Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer 42:717–727.
Sombroek, C. C., Stam, A. G., Masterson, A. J., Lougheed, S. M., Schakel, M. J., Meijer, C. J., Pinedo, H. M., van den Eertwegh, A. J., Scheper, R. J. and de Gruijl, T. D. 2002. Prostanoids play a major role in the primary tumor-induced inhibition of dendritic cell differentiation. J Immunol 168:4333–4343.
Stary, G., Bangert, C., Tauber, M., Strohal, R., Kopp, T. and Stingl, G. 2007. Tumoricidal activity of TLR7/8-activated inflammatory dendritic cells. J Exp Med 204:1441–1451.
Strieter, R. M., Burdick, M. D., Mestas, J., Gomperts, B., Keane, M. P. and Belperio, J. A. 2006. Cancer CXC chemokine networks and tumour angiogenesis. Eur J Cancer 42:768–778.
Talmadge, J. E., Donkor, M. and Scholar, E. 2007. Inflammatory cell infiltration of tumors: Jekyll or Hyde. Cancer Metastasis Rev 26:373–400.
Tan, T. T. and Coussens, L. M. 2007. Humoral immunity, inflammation and cancer. Curr Opin Immunol 19:209–216.
Tesniere, A., Panaretakis, T., Kepp, O., Apetoh, L., Ghiringhelli, F., Zitvogel, L. and Kroemer, G. 2008. Molecular characteristics of immunogenic cancer cell death. Cell Death Differ 15:3–12.
Torres, D., Paget, C., Fontaine, J., Mallevaey, T., Matsuoka, T., Maruyama, T., Narumiya, S., Capron, M., Gosset, P., Faveeuw, C. and Trottein, F. 2008. Prostaglandin D2 inhibits the production of IFN-gamma by invariant NK T cells: consequences in the control of B16 melanoma. J Immunol 180:783–792.
Viorritto, I. C., Nikolov, N. P. and Siegel, R. M. 2007. Autoimmunity versus tolerance: can dying cells tip the balance? Clin Immunol 122:125–134.
Ward, R. C. and Kaufman, H. L. 2007. Targeting costimulatory pathways for tumor immunotherapy. Int Rev Immunol 26:161–196.
Xu, J., Chakrabarti, A. K., Tan, J. L., Ge, L., Gambotto, A. and Vujanovic, N. L. 2007. Essential role of the TNF-TNFR2 cognate interaction in mouse dendritic cell-natural killer cell crosstalk. Blood 109:3333–3341.
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Pos, Z., Sabatino, M., Spivey, T., Liu, H., Falus, A., Marincola, F.M. (2009). Tumor-Associated Inflammation and Impact on Dendritic Cell Function. In: Salter, R., Shurin, M. (eds) Dendritic Cells in Cancer. Springer, New York, NY. https://doi.org/10.1007/978-0-387-88611-4_11
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