Abstract
Smoldering, nonresolving inflammation is part of the tumor microenvironment (Balkwill and Mantovani 2001; Coussens and Werb 2002; Mantovani et al. 2008a). Inflammatory cells and mediators are present in the microenvironment of cancers epidemiologically related or unrelated to inflammatory or infectious conditions. Leukocyte infiltration and the presence of soluble mediators such as cytokines, and chemokines are key characteristics of CRI. Conditions predisposing to cancer (e.g., inflammatory bowel disease, IBD) or genetic events that cause neoplastic transformation orchestrate the construction of an inflammatory microenvironment. Indeed, alterations of oncogenes drive the production of inflammatory mediators. Thus, an intrinsic pathway of inflammation (driven in tumor cells), as well as an extrinsic pathway driven by chronic inflammatory conditions have been identified, both of which contribute to tumor progression (Mantovani et al.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Andreu, P., Johansson, M., Affara, N. I., Pucci, F., Tan, T., Junankar, S., Korets, L., Lam, J., Tawfik, D., DeNardo, D. G., Naldini, L., de Visser, K., De Palma, M. and Coussens, L. M. (2010). FcRgamma activation regulates inflammation-associated squamous carcinogenesis. Cancer Cell 17: 121–134.
Apetoh, L., Ghiringhelli, F., Tesniere, A., Obeid, M., Ortiz, C., Criollo, A., Mignot, G., Maiuri, M. C., Ullrich, E., Saulnier, P., Yang, H., Amigorena, S., Ryffel, B., Barrat, F. J., Saftig, P., Levi, F., Lidereau, R., Nogues, C., Mira, J. P., Chompret, A., Joulin, V., Clavel-Chapelon, F., Bourhis, J., Andre, F., Delaloge, S., Tursz, T., Kroemer, G. and Zitvogel, L. (2007). Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med 13: 1050–1059.
Aspord, C., Pedroza-Gonzalez, A., Gallegos, M., Tindle, S., Burton, E. C., Su, D., Marches, F., Banchereau, J. and Palucka, A. K. (2007). Breast cancer instructs dendritic cells to prime interleukin 13-secreting CD4+ T cells that facilitate tumor development. J Exp Med 204: 1037–1047.
Balkwill, F. and Mantovani, A. (2001). Inflammation and cancer: back to Virchow? Lancet 357: 539–545.
Berek, J. S., Schultes, B. C. and Nicodemus, C. F. (2003). Biologic and immunologic therapies for ovarian cancer. J Clin Oncol 21: 168s–174s.
Bottazzi, B., Polentarutti, N., Acero, R., Balsari, A., Boraschi, D., Ghezzi, P., Salmona, M. and Mantovani, A. (1983). Regulation of the macrophage content of neoplasms by chemoattractants. Science 220: 210–212.
Colombo, N., Peccatori, F., Paganin, C., Bini, S., Brandely, M., Mangioni, C., Mantovani, A. and Allavena, P. (1992). Anti-tumor and immunomodulatory activity of intraperitoneal IFN-gamma in ovarian carcinoma patients with minimal residual tumor after chemotherapy. Int J Cancer 51: 42–46.
Coussens, L. M. and Werb, Z. (2002). Inflammation and cancer. Nature 420: 860–867.
De Palma, M., Murdoch, C., Venneri, M. A., Naldini, L. and Lewis, C. E. (2007). Tie2-expressing monocytes: regulation of tumor angiogenesis and therapeutic implications. Trends Immunol 28: 519–524.
de Visser, K. E., Korets, L. V. and Coussens, L. M. (2005). De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent. Cancer Cell 7: 411–423.
DeNardo, D. G., Barreto, J. B., Andreu, P., Vasquez, L., Tawfik, D., Kolhatkar, N. and Coussens, L. M. (2009). CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell 16: 91–102.
Duluc, D., Corvaisier, M., Blanchard, S., Catala, L., Descamps, P., Gamelin, E., Ponsoda, S., Delneste, Y., Hebbar, M. and Jeannin, P. (2009). Interferon-gamma reverses the immunosuppressive properties and prevents the generation of human tumor-associated macrophages. Int J Cancer 125: 367–373.
Erler, J. T., Bennewith, K. L., Cox, T. R., Lang, G., Bird, D., Koong, A., Le, Q. T. and Giaccia, A. J. (2009). Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell 15: 35–44.
Fridlender, Z. G., Sun, J., Kim, S., Kapoor, V., Cheng, G., Ling, L., Worthen, G. S. and Alberlda, S. M. (2009). Polarization of tumor-associated neutrophil (TAN) phenotype by TGF-beta: “N1” versus “N2” TAN – a new paradigm? Cancer Cell 16: 183–194.
Ghiringhelli, F., Apetoh, L., Tesniere, A., Aymeric, L., Ma, Y., Ortiz, C., Vermaelen, K., Panaretakis, T., Mignot, G., Ullrich, E., Perfettini, J. L., Schlemmer, F., Tasdemir, E., Uhl, M., Genin, P., Civas, A., Ryffel, B., Kanellopoulos, J., Tschopp, J., Andre, F., Lidereau, R., McLaughlin, N. M., Haynes, N. M., Smyth, M. J., Kroemer, G. and Zitvogel, L. (2009). Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Nat Med 15: 1170–1178.
Hagemann, T., Wilson, J., Burke, F., Kulbe, H., Li, N. F., Pluddemann, A., Charles, K., Gordon, S. and Balkwill, F. R. (2006). Ovarian cancer cells polarize macrophages toward a tumor-associated phenotype. J Immunol 176: 5023–5032.
Hagemann, T., Wilson, J., Kulbe, H., Li, N. F., Leinster, D. A., Charles, K., Klemm, F., Pukrop, T., Binder, C. and Balkwill, F. R. (2005). Macrophages induce invasiveness of epithelial cancer cells via NF-kappa B and JNK. J Immunol 175: 1197–1205.
Kaplan, R. N., Riba, R. D., Zacharoulis, S., Bramley, A. H., Vincent, L., Costa, C., MacDonald, D. D., Jin, D. K., Shido, K., Kerns, S. A., Zhu, Z., Hicklin, D., Wu, Y., Port, J. L., Altorki, N., Port, E. R., Ruggero, D., Shmelkov, S. V., Jensen, K. K., Rafii, S. and Lyden, D. (2005). VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438: 820–827.
Kim, S., Takahashi, H., Lin, W.-W., Descargues, P., Grivennikov, S., Kim, Y., Luo, J.-L. and Karin, M. (2009). Carcinoma produced factors activate myeloid cells via TLR2 to stimulate metastasis. Nature 457: 102–106.
Kryczek, I., Banerjee, M., Cheng, P., Vatan, L., Szeliga, W., Wei, S., Huang, E., Finlayson, E., Simeone, D., Welling, T. H., Chang, A., Coukos, G., Liu, R. and Zou, W. (2009). Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood 114: 1141–1149.
Kuang, D. M., Wu, Y., Chen, N., Cheng, J., Zhuang, S. M. and Zheng, L. (2007). Tumor-derived hyaluronan induces formation of immunosuppressive macrophages through transient early activation of monocytes. Blood 110: 587–595.
Kulbe, H., Thompson, R., Wilson, J. L., Robinson, S., Hagemann, T., Fatah, R., Gould, D., Ayhan, A. and Balkwill, F. (2007). The inflammatory cytokine tumor necrosis factor-alpha generates an autocrine tumor-promoting network in epithelial ovarian cancer cells. Cancer Res 67: 585–592.
Luo, Y., Zhou, H., Krueger, J., Kaplan, C., Lee, S. H., Dolman, C., Markowitz, D., Wu, W., Liu, C., Reisfeld, R. A. and Xiang, R. (2006). Targeting tumor-associated macrophages as a novel strategy against breast cancer. J Clin Invest 116: 2132–2141.
Mantovani, A. (1999). The chemokine system: redundancy for robust outputs. Immunol Today 20: 254–257.
Mantovani, A., Bonecchi, R., Locati, M. (2006). Tuning inflammation and immunity by chemokine sequestration: decoys and more. Nature Reviews in Immunology 12: 907–918.
Mantovani, A. (2009). Cancer: inflaming metastasis Nature 457: 36–37.
Mantovani, A., Allavena, P., Sica, A. and Balkwill, F. (2008a). Cancer-related inflammation. Nature 454: 436–444.
Mantovani, A., Bottazzi, B., Colotta, F., Sozzani, S. and Ruco, L. (1992). The origin and function of tumor-associated macrophages. Immunol Today 13: 265–270.
Mantovani, A., Romero, P., Paluka, A. and Marincola, F. (2008b). Tumor immunity: effector response to tumor and the influence of the microenvironment. Lancet 371: 771–783.
Mantovani, A., Sozzani, S., Locati, M., Allavena, P. and Sica, A. (2002). Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 23: 549–555.
Marttila-Ichihara, F., Auvinen, K., Elima, K., Jalkanen, S. and Salmi, M. (2009). Vascular adhesion protein-1 enhances tumor growth by supporting recruitment of Gr-1+CD11b+ myeloid cells into tumors. Cancer Res 69: 7875–7883.
Nibbs, R. J., Gilchrist, D. S., King, V., Ferra, A., Forrow, S., Hunter, K. D. and Graham, G. J. (2007). The atypical chemokine receptor D6 suppresses the development of chemically induced skin tumors. J Clin Invest 117: 1884–1892.
Nickoloff, B. J., Ben-Neriah, Y. and Pikarsky, E. (2005). Inflammation and cancer: is the link as simple as we think? J Invest Dermatol 124: x-xiv.
Pollard, J. W. (2009). Trophic macrophages in development and disease. Nat Rev Immunol 9: 259–270.
Popivanova, B. K., Kostadinova, F. I., Furuichi, K., Shamekh, M. M., Kondo, T., Wada, T., Egashira, K. and Mukaida, N. (2009). Blockade of a chemokine, CCL2, reduces chronic colitis-associated carcinogenesis in mice. Cancer Res 69: 7884–7892.
Porta, C., Rimoldi, M., Raes, G., Brys, L., Ghezzi, P., Di Liberto, D., Dieli, F., Ghisletti, S., Natoli, G., De Baetselier, P., Mantovani, A. and Sica, A. (2009). Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor kappaB. Proc Natl Acad Sci U S A 106: 14978–14983.
Ritchie, D. S. and Smyth, M. J. (2009). A new therapeutic target for leukemia comes to the surface. Cell 138: 226–228.
Roca, H., Varsos, Z. S., Sud, S., Craig, M. J., Ying, C. and Pienta, K. J. (2009). CCL2 and IL-6 promote survival of human CD11b+- peripheral blood mononuclear cells and induce M2-type macrophage polarization. J Biol Chem 284: 34342–34354.
Song, L., Asgharzadeh, S., Salo, J., Engell, K., Wu, H. W., Sposto, R., Ara, T., Silverman, A. M., DeClerck, Y. A., Seeger, R. C. and Metelitsa, L. S. (2009). Valpha24-invariant NKT cells mediate antitumor activity via killing of tumor-associated macrophages. J Clin Invest 119: 1524–1536.
Torroella-Kouri, M., Silvera, R., Rodriguez, D., Caso, R., Shatry, A., Opiela, S., Ilkovitch, D., Schwendener, R. A., Iragavarapu-Charyulu, V., Cardentey, Y., Strbo, N. and Lopez, D. M. (2009). Identification of a subpopulation of macrophages in mammary tumor-bearing mice that are neither M1 nor M2 and are less differentiated. Cancer Res 69: 4800–4809.
Vetrano, S., Borroni, E. M., Sarukhan, A., Savino, B., Bonecchi, R., Correale, C., Arena, V., Fantini, M., Roncalli, M., Malesci, A., Mantovani, A., Locati, M. and Danese, S. (2010). The lymphatic system controls intestinal inflammation and inflammation-associated colon cancer through the chemokine decoy receptor D6. Gut 59: 197–206.
Wallace, K. L., Marshall, M. A., Ramos, S. I., Lannigan, J. A., Field, J. J., Strieter, R. M. and Linden, J. (2009). NKT cells mediate pulmonary inflammation and dysfunction in murine sickle cell disease through production of IFN-gamma and CXCR3 chemokines. Blood 114: 667–676.
Wels, J., Kaplan, R. N., Rafii, S. and Lyden, D. (2008). Migratory neighbors and distant invaders: tumor-associated niche cells. Genes Dev 22: 559–574.
Windbichler, G. H., Hausmaninger, H., Stummvoll, W., Graf, A. H., Kainz, C., Lahodny, J., Denison, U., Muller-Holzner, E. and Marth, C. (2000). Interferon-gamma in the first-line therapy of ovarian cancer: a randomized phase III trial. Br J Cancer 82: 1138–1844.
Wyckoff, J. B., Wang, Y., Lin, E. Y., Li, J. F., Goswami, S., Stanley, E. R., Segall, J. E., Pollard, J. W. and Condeelis, J. (2007). Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. Cancer Res 67: 2649–2656.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Mantovani, A., Garlanda, C., Allavena, P., Sica, A., Locati, M. (2011). The Yin Yang of Cancer Related Inflammation. In: Marincola, F., Wang, E. (eds) Immunologic Signatures of Rejection. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7219-4_2
Download citation
DOI: https://doi.org/10.1007/978-1-4419-7219-4_2
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4419-7218-7
Online ISBN: 978-1-4419-7219-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)