Abstract
There is increasing evidence that the immune cells within the tumor microenvironment play a key role in the ability of tumor cells to proliferate and spread. Given that macrophages are the most frequent hematopoietic cells found in the tumor microenvironment, they play an especially important part in tumor biology. There are numerous mechanisms by which tumor-associated innate immune cells can influence most aspects of the metastatic process. They play a role in the epithelial to mesenchymal transformation occurring in the original tumor cells and enhance basement membrane breakdown by the cancer cells invading neighboring tissue, lymph nodes, and blood vessels. Tumor-associated innate immune cells have been shown to have a crucial role in angiogenesis, in immunosuppression, and eventually in priming distant sites for the development of metastases. Unfortunately, we still know relatively little about the roles of these cells in lung cancer. Further work in animal models and using patient lung cancer samples is very much needed. With this knowledge, a better understanding of the role that these cells play in the metastatic process may facilitate development of new therapeutics, as well as the recognition of new diagnostic and prognostic markers. Modulation of the metastatic phenotype through intervention in the host innate immune response remains a promising future area of cancer therapy.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Gupta, G.P. and Massague, J. 2006. Cancer metastasis: Building a framework. Cell 127: 679–695.
Virchow, R. 1863. Aetologie der neoplastichen geschwulste/pathogenie der neoplastichen geschwulste In Die krankhaften geschwulste (Berlin: Verlag von August Hirschwald; reprint).
Pollard, J. 2004. Tumour-educated macrophages promote tumour progression and metastasis. Nat. Rev. Cancer 4: 71–78.
Murdoch, C., Giannoudis, A., and Lewis, C.E. 2004. Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissues. Blood 104: 2224–2234.
Luboshits, G., Shina, S., Kaplan, O., Engelberg, S., Nass, D., Lifshitz-Mercer, B., Chaitchik, S., Keydar, I., and Ben-Baruch, A. 1999. Elevated expression of the CC chemokine regulated on activation, normal T cell expressed and secreted (RANTES) in advanced breast carcinoma. Cancer Res. 59: 4681–4687.
Ueno, T., Toi, M., Saji, H., Muta, M., Bando, H., Kuroi, K., Koike, M., Inadera, H., and Matsushima, K. 2000. Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer. Clin. Cancer Res. 6: 3282–3289.
Scotton, C., Milliken, D., Wilson, J., Raju, S., and Balkwill, F. 2001. Analysis of CC chemokine and chemokine receptor expression in solid ovarian tumours. Brit. J. Cancer 85: 891.
Balkwill, F. 2003. Chemokine biology in cancer. Semin. Immunol. 15: 49–55.
Muller, A., Homey, B., Soto, H., Ge, N., Catron, D., Buchanan, M.E., Mcclanahan, T., Murphy, E., Yuan, W., Wagner, S.N., Barrera, J.L., Mohar, A., Verastegui, E., and Zlotnik, A. 2001. Involvement of chemokine receptors in breast cancer metastasis. Nature 410: 50–56.
Scotton, C.J., Wilson, J.L., Scott, K., Stamp, G., Wilbanks, G.D., Fricker, S., Bridger, G., and Balkwill, F.R. 2002. Multiple actions of the chemokine CXCL2 on epithelial tumor cells in human ovarian cancer. Cancer Res. 62: 5930–5938.
Phillips, R.J., Burdick, M.D., Lutz, M., Belperio, J.A., Keane, M.P., and Strieter, R.M. 2003. The stromal derived factor-1/CXCL12-CXC chemokine receptor 4 biological axis in non-small cell lung cancer metastases. Am. J. Respir. Crit. Care Med. 167: 1676–1686.
Biswas, S.K., Sica, A., and Lewis, C.E. 2008. Plasticity of macrophage function during tumor progression: Regulation by distinct molecular mechanisms. J. Immunol. 180: 2011–2017.
Keller, R, K.R., Keist, R., Wechsler, A., Leist, T.P., and van der Meide, P.H. 1990. Mechanisms of macrophage-mediated tumor cell killing: A comparative analysis of the roles of reactive nitrogen intermediates and tumor necrosis factor. Int. J. Cancer 46: 682–686.
Martin, J.H. and Edwards, S.W. 1993. Changes in mechanisms of monocyte/macrophage-mediated cytotoxicity during culture. Reactive oxygen intermediates are involved in monocyte- mediated cytotoxicity, whereas reactive nitrogen intermediates are employed by macrophages in tumor cell killing. J. Immunol. 150: 3478–3486.
Grabstein, K.H., Urdal, D.L., Tushinski, R.J., Mochizuki, D.Y, Price, V.L., Cantrell, M.A., Gillis, S., and Conlon, P.J. 1986. Induction of macrophage tumoricidal activity by granulocyte-macrophage colony-stimulating factor. Science 232: 506–508.
Kamimura, A., Kamachi, M., Nishihira, J., Ogura, S., Isobe, H., Dosaka-Akita, H., Ogata, A., Shindoh, M., Ohbuchi, T., and Kawakami, Y. 2000. Intracellular distribution of macrophage migration inhibitory factor predicts the prognosis of patients with adenocarcinoma of the lung. Cancer 89: 334–341.
Janat-Amsbury, M.M., Yockman, J.W., Lee, M., Kern, S., Furgeson, D.Y., Bikram, M., and Kim, S.W. 2004. Combination of local, nonviral IL-12 gene therapy and systemic paclitaxel treatment in a metastatic breast cancer model. Mol. Ther. 9: 829–836.
Li, Q., Carr, A.L., Donald, E.J., Skitzki, J.J., Okuyama, R., Stoolman, L.M., and Chang, A.E. 2005. Synergistic effects of IL-12 and IL-18 in skewing tumor-reactive T-cell responses towards a type 1 pattern. Cancer Res. 65: 1063–1070.
Lewis, C.E. and Pollard, J.W. 2006. Distinct role of macrophages in different tumor microenvironments. Cancer Res. 66: 605–612.
Coussens, L.M. and Werb, Z. 2002. Inflammation and cancer. Nature 420: 860–867.
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.
Stout, R.D., Jiang, C., Matta, B., Tietzel, I., Watkins, S.K., and Suttles, J. 2005. Macrophages sequentially change their functional phenotype in response to changes in microenvironmental influences. J. Immunol. 175: 342–349.
Mills, C.D., Kincaid, K., Alt, J.M., Heilman, M.J., and Hill, A.M. 2000. M-1/m-2 macrophages and the TH1/TH2 paradigm. J. Immunol. 164: 6166–6173.
Munder, M., Eichmann, K., and Modolell, M. 1998. Alternative metabolic states in murine macrophages reflected by the nitric oxide synthase/arginase balance: Competitive regulation by CD4+ t cells correlates with TH1/TH2 phenotype. J. Immunol. 160: 5347–5354.
Bonecchi, R., Sozzani, S., Stine, J.T., Luini, W., D’amico, G., Allavena, P., Chantry, D., and Mantovani, A. 1998. Divergent effects of interleukin-4 and interferon-gamma on macrophage-derived chemokine production: An amplification circuit of polarized T helper 2 responses. Blood 92: 2668–2671.
Lewis, J.S., Landers, R.J., Underwood, J.C.E., Harris, A.L., and Lewis, C.E. 2000. Expression of vascular endothelial growth factor by macrophages is up-regulated in poorly vascularized areas of breast carcinomas. J. Pathol. 192: 150–158.
Welch, D.R., Schissel, D.J., Howrey, R.P., and Aeed, P.A. 1989. Tumor-elicited polymorphonuclear cells, in contrast to ``normal'' circulating polymorphonuclear cells, stimulate invasive and metastatic potentials of rat mammary adenocarcinoma cells. Proc. Natl. Acad. Sci. 86: 5859–5863.
Heifets, L. 1982. Centennial of Metchnikoff’s discovery. J. Reticuloendothel Soc. 31: 381–391.
Di Carlo, E., Forni, G., Lollini, P., Colombo, M.P., Modesti, A., and Musiani, P. 2001. The intriguing role of polymorphonuclear neutrophils in antitumor reactions. Blood 97: 339–345.
Ishihara, Y.F.T., Iijima, H., Saito, K., Matsunaga, K. 1998. The role of neutrophils as cytotoxic cells in lung metastasis: Suppression of tumor cell metastasis by a biological response modifier (psk). In Vivo 12: 175–182.
Ishihara, Y.I.H. and Matsunaga, K. 1998. Contribution of cytokines on the suppression of lung metastasis. Biotherapy 11: 267–275.
Scapini, P., Lapinet-Vera, J.A., Gasperini, S., Calzetti, F., Bazzoni, F., and Cassatella, M.A. 2000. The neutrophil as a cellular source of chemokines. Immunol. Rev. 177: 195–203.
Wu, Q.D., Wang, J.H., Condron, C., Bouchier-Hayes, D., and Redmond, H.P. 2001. Human neutrophils facilitate tumor cell transendothelial migration. Am. J. Physiol. Cell Physiol. 280: C814–822.
Orr, F.W. and Warner, D.J.A. 1990. Effects of systemic complement activation and neutrophil-mediated pulmonary injury on the retention and metastasis of circulating cancer cells in mouse lungs. Lab. Invest. 62: 331–338.
Orr, F.W. and Warner, D.J.A. 2001. Tumor cell interactions with the microvasculature: A rate-limiting step in metastasis. Surg. Oncol. Clin. N. Am. 10: 357–381.
Doi, K., Horiuchi, T., Uchinami, M., Tabo, T., Kimura, N., Yokomachi, J., Yoshida, M., and Tanaka, K. 2002. Neutrophil elastase inhibitor reduces hepatic metastases induced by ischaemia-reprefusion in rats. Eur. J. Surg. 168: 507.
Aeed, P.A., Nakajima, M., and Welch, D.R. 1988. The role of polymorphonuclear leukocytes (PMN) on the growth and metastatic potential of 13762nf mammary adenocarcinoma cells. Int. J. Cancer 42: 748–759.
Nozawa, H., Chiu, C., and Hanahan, D. 2006. Infiltrating neutrophils mediate the initial angiogenic switch in a mouse model of multistage carcinogenesis. Proc. Natl. Acad. Sci. 103: 12493–12498.
Schmielau, J. and Finn, O.J. 2001. 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.
Zea, A.H., Rodriguez, P.C., Atkins, M.B., Hernandez, C., Signoretti, S., Zabaleta, J., McDermott, D., Quiceno, D., Youmans, A., O’neill, A., Mier, J., and Ochoa, A.C. 2005. Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: A mechanism of tumor evasion. Cancer Res. 65: 3044–3048.
Schmidt, H., Bastholt, L., Geertsen, P., Christensen, I.J., Larsen, S., Gehl, J., and Von Der Maase, H. 2005. Elevated neutrophil and monocyte counts in peripheral blood are associated with poor survival in patients with metastatic melanoma: A prognostic model. Brit. J. Cancer 93: 273–278.
McGary, C.T., Miele, M.F., and Welch, D.R. 1995. Highly metastatic 13762NF rat mammary adenocarcinoma cell clones stimulate bone marrow by secretion of granulocyte-macrophage colony-stimulating factor/interleukin-3 activity. Am. J. Pathol. 147: 1668–1681.
De Larco, J.E., Wuertz, B.R.K., and Furcht, L.T. 2004. The potential role of neutrophils in promoting the metastatic phenotype of tumors releasing interleukin-8. Clin. Cancer Res. 10: 4895–4900.
De Larco, J.E., Wuertz, B.R.K., Yee, D., Rickert, B.L., and Furcht, L.T. 2003. Atypical methylation of the interleukin-8 gene correlates strongly with the metastatic potential of breast carcinoma cells. Proc. Natl. Acad. Sci. 100: 13988–13993.
Caruso, R.A., Bellocco, R., Pagano, M., Bertoli, G., Rigoli, L., and Inferrera, C. 2002. Prognostic value of intratumoral neutrophils in advanced gastric carcinoma in a high-risk area in northern Italy. Mod. Pathol. 15: 831–837.
Gregoire, C., Chasson, L., Luci, C., Tomasello, E., Geissmann, F., Vivier, E., and Walzer, T. 2007. The trafficking of natural killer cells. Immunol. Rev. 220: 169–182.
Yang, Q., Goding, S., Hokland, M., and Basse, P. 2006. Antitumor activity of NK cells. Immunol. Res. 36: 13–25.
Lu, L.-M., Zavitz, C.C.J., Chen, B., Kianpour, S., Wan, Y., and Stampfli, M.R. 2007. Cigarette smoke impairs NK cell-dependent tumor immune surveillance. J. Immunol. 178: 936–943.
Ribatti, D., Crivellato, E., Roccaro, A.M., Ria, R., and Vacca, A. 2004. Mast cell contribution to angiogenesis related to tumour progression. Clin. Exper. Allergy 34: 1660–1664.
Tomita, M., Matsuzaki, Y., and Onitsuka, T. 2000. Effect of mast cells on tumor angiogenesis in lung cancer. Ann. Thorac. Surg. 69: 1686–1690.
Azizkhan, R.G., Azizkhan, J.C., Zetter, B.R., and Folkman, J. 1980. Mast cell heparin stimulates migration of capillary endothelial cells in vitro. J. Exp. Med. 152: 931–944.
Tomita, M., Matsuzaki, Y., Edagawa, M., Shimizu, T., Hara, M., and Onitsuka, T. 2003. Distribution of mast cells in mediastinal lymph nodes from lung cancer patients. World J. Surg. Oncol. 1: 25.
Ibaraki, T., Muramatsu, M., Takai, S., Jin, D., Maruyama, H., Orino, T., Katsumata, T., and Miyazaki, M. 2005. The relationship of tryptase- and chymase-positive mast cells to angiogenesis in stage 1 non-small cell lung cancer. Eur. J. Cardio-Thorac. Surg. 28: 617–621.
Akhurst, R.J. and Derynck, R. 2001. TGF-β signaling in cancer – a double-edged sword. Trends Cell Biol. 11: S44–S51.
Ashley, D.M., Kong, F.M., Bigner, D.D., and Hale, L.P. 1998. Endogenous expression of transforming growth factor beta-1 inhibits growth and tumorigenicity and enhances fas-mediated apoptosis in a murine high-grade glioma model. Cancer Res. 58: 302–309.
Wrzesinski, S.H., Wan, Y.Y., and Flavell, R.A. 2007. Transforming growth factor-β and the immune response: Implications for anticancer therapy. Clin Cancer Res. 13: 5262–5270.
Bacman, D., Merkel, S., Croner, R., Papadopoulos, T., Brueckl, W., and Dimmler, A. 2007. TGF-beta receptor 2 downregulation in tumour-associated stroma worsens prognosis and high-grade tumours show more tumour-associated macrophages and lower TGF-beta1 expression in colon carcinoma: A retrospective study. BMC Cancer 7: 156.
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 NFκB and JNK. J. Immunol. 175: 1197–1205.
Wyckoff, J., Wang, W., Lin, E.Y., Wang, Y., Pixley, F., Stanley, E.R., Graf, T., Pollard, J.W., Segall, J., and Condeelis, J. 2004. A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res. 64: 7022–7029.
Domagala, W.S.G., Szadowska, A., Dukowicz, A., Weber, K., and Osborn, M. 1992. Cathepsin B in invasive ductal nos breast carcinoma as defined by immunohistochemistry. No correlation with survival at 5 years. Am. J. Pathol. 141: 1003–1012.
Hagemann, T., Robinson, S.C., Schulz, M., Trumper, L., Balkwill, F.R., and Binder, C. 2004. Enhanced invasiveness of breast cancer cell lines upon co-cultivation with macrophages is due to TNF-α dependent up-regulation of matrix metalloproteases. Carcinogenesis 25: 1543–1549.
Hiratsuka, S., Nakamura, K., Iwai, S., Murakami, M., Itoh, T., Kijima, H., Shipley, J.M., Senior, R.M., and Shibuya, M. 2002. Mmp9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis. Cancer Cell 2: 289–300.
Chen, X., Su, Y., Fingleton, B., Acuff, H., Matrisian, L.M., Zent, R., and Pozzi, A. 2005. Increased plasma MMP9 in integrin α1-null mice enhances lung metastasis of colon carcinoma cells. Int. J. Cancer 116: 52–61.
Williams, T.M., Medina, F., Badano, I., Hazan, R.B., Hutchinson, J., Muller, W.J., Chopra, N.G., Scherer, P.E., Pestell, R.G., and Lisanti, M.P. 2004. Caveolin-1 gene disruption promotes mammary tumorigenesis and dramatically enhances lung metastasis in vivo: Role of cav-1 in cell invasiveness and matrix metalloproteinase (MMP-2/9) secretion. J. Biol. Chem. 279: 51630–51646.
Zhongyun Dong, R.K., Xiulan, Y., and Fidler, I.J. 1997. Macrophage-derived metalloelastase is responsible for the generation of angiostatin in Lewis lung carcinoma. Cell 88: 801–810.
Koide, N., Nishio, A., Sato, T., Sugiyama, A., and Miyagawa, S. 2004. Significance of macrophage infiltration in squamous cell carcinoma of the esophagus. Am. J. Gastroenterol. 99: 1667–1674.
Takanami, T., Takeuchi, K., and Kodaira, S. 1999. Tumor-associated macrophage infiltration in pulmonary adenocarcinoma: Association with angiogenesis and poor prognosis. Oncology 57: 138–142.
Koukourakis Mi, G.A., Kakolyris, S., O’Byrne, K.J., Apostolikas, N., Skarlatos, J., Gatter, K.C., andHarris A.L. 1998. Different patterns of stromal and cancer cell thymidine phosphorylase reactivity in non-small-cell lung cancer: Impact on tumour neoangiogenesis and survival. Brit. J. Cancer. 77: 1696–1703.
Barleon, B., Sozzani, S., Zhou, D., Weich, H.A., Mantovani, A., and Marme, D. 1996. Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1. Blood 87: 3336–3343.
Robinson-Smith, T.M., Isaacsohn, I., Mercer, C.A., Zhou, M., Van Rooijen, N., Husseinzadeh, N., Mcfarland-Mancini, M.M., and Drew, A.F. 2007. Macrophages mediate inflammation-enhanced metastasis of ovarian tumors in mice. Cancer Res. 67: 5708–5716.
Queen, M.M., Ryan, R.E., Holzer, R.G., Keller-Peck, C.R., and Jorcyk, C.L. 2005. Breast cancer cells stimulate neutrophils to produce oncostatin M: Potential implications for tumor progression. Cancer Res. 65: 8896–8904.
Li, A., Dubey, S., Varney, M.L., Dave, B.J., and Singh, R.K. 2003. IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis. J. Immunol. 170: 3369–3376.
White, E.S., Strom, S.R.B., Wys, N.L., and Arenberg, D.A. 2001. Non-small cell lung cancer cells induce monocytes to increase expression of angiogenic activity. J. Immunol. 166: 7549–7555.
White, E.S., Flaherty, K.R., Carskadon, S., Brant, A., Iannettoni, M.D., Yee, J., Orringer, M.B., and Arenberg, D.A. 2003. Macrophage migration inhibitory factor and cxc chemokine expression in non-small cell lung cancer: Role in angiogenesis and prognosis. Clin. Cancer Res. 9: 853–860.
Schoppmann, S.F., Birner, P., Stockl, J., Kalt, R., Ullrich, R., Caucig, C., Kriehuber, E., Nagy, K., Alitalo, K., and Kerjaschki, D. 2002. Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis. Am. J. Pathol. 161: 947–956.
Leek, R.D. and Lewis, C.L. 1999. Necrosis correlates with high vascular density and focal macrophage infiltration in invasive carcinoma of the breast. Brit. J. Cancer 79: 991–995.
Leek, R.D., Hunt, N.C., Landers, R.J., Lewis, C.E., Royds, J.A., and Harris, A.L. 2000. Macrophage infiltration is associated with VEGF and EGFR expression in breast cancer. J. Pathol. 190: 430–436.
Dinapoli, M.R., Calderon, C.L., and Lopez, D.M. 1996. The altered tumoricidal capacity of macrophages isolated from tumor- bearing mice is related to reduce expression of the inducible nitric oxide synthase gene. J. Exp. Med. 183: 1323–1329.
Sica, A., Saccani, A., Bottazzi, B., Polentarutti, N., Vecchi, A., Damme, J.V., and Mantovani, A. 2000. Autocrine production of il-10 mediates defective IL-12 production and NFκB activation in tumor-associated macrophages. J. Immunol. 164: 762–767.
Li, M.O., Wan, Y.Y., Sanjabi, S., Robertson, A.-K.L., and Flavell, R.A. 2006. Transforming growth factor-β; regulation of immune responses. Ann. Rev. Immunol. 24: 99–146.
Teicher, B.A. 2007. Transforming growth factor-β and the immune response to malignant disease. Clin. Cancer Res. 13: 6247–6251.
Rodriguez, P.C., Quiceno, D.G., Zabaleta, J., Ortiz, B., Zea, A.H., Piazuelo, M.B., Delgado, A., Correa, P., Brayer, J., Sotomayor, E.M., Antonia, S., Ochoa, J.B., and Ochoa, A.C. 2004. Arginase 1 production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses. Cancer Res. 64: 5839–5849.
Mrass, P. and Weninger, W. 2006. Immune cell migration as a means to control immune privilege: Lessons from the CNS and tumors. Immunol. Rev. 213: 195–212.
Kobie, J.J., Wu, R.S., Kurt, R.A., Lou, S., Adelman, M.K., Whitesell, L.J., Ramanathapuram, L.V., Arteaga, C.L., and Akporiaye, E.T. 2003. Transforming growth factor–β inhibits the antigen-presenting functions and antitumor activity of dendritic cell vaccines. Cancer Res. 63: 1860–1864.
Marie, J.C., Letterio, J.J., Gavin, M., and Rudensky, A.Y. 2005. TGF-²1 maintains suppressor function and foxp3 expression in CD4+CD25+ regulatory T cells. J. Exp. Med. 201: 1061–1067.
Liu, V.C., Wong, L.Y., Jang, T., Shah, A.H., Park, I., Yang, X., Zhang, Q., Lonning, S., Teicher, B.A., and Lee, C. 2007. Tumor evasion of the immune system by converting CD4+CD25– T-cells into CD4+CD25+ T regulatory cells: Role of tumor-derived TGF-β. J. Immunol. 178: 2883–2892.
Chang, C.-J., Liao, C.-H., Wang, F.-H., and Lin, C.-M. 2003. Transforming growth factor-β² induces apoptosis in antigen-specific CD4+ T cells prepared for adoptive immunotherapy. Immunol. Lett. 86: 37–43.
Thomas, D.A. and Massague, J. 2005. TGF-β directly targets cytotoxic T cell functions during tumor evasion of immune surveillance. Cancer Cell 8: 369–380.
Ahmadzadeh, M. and Rosenberg, S.A. 2005. TGF-β1 attenuates the acquisition and expression of effector function by tumor antigen-specific human memory CD8 T cells. J. Immunol. 174: 5215–5223.
Jakobisiak, M., Lasek, W., and Golab, J. 2003. Natural mechanisms protecting against cancer. Immunol. Lett. 90: 103–122.
Hanna, N. 1982. Role of natural killer cells in control of cancer metastasis. Cancer Metastasis Rev. 1: 45–64.
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.
Hiratsuka, S., Watanabe, A., Aburatani, H., and Maru, Y. 2006. Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nat. Cell Biol. 8: 1369–1375.
Oberg, A., Samii, S., Stenling, R., and Lindmark, G. 2002. Different occurrence of cd8+, CD45R0+, and CD68+ immune cells in regional lymph node metastases from colorectal cancer as potential prognostic predictors. Int. J. Colorectal Dis. 17: 25–29.
Lin, E.Y., Nguven, A.V., Russell, R.G., and Pollard J.W. 2001. Colony stimulating factor 1 promotes progression of mammary tumors to malignancy. J. Exp. Med. 193: 727–740.
Yano, S., Nishioka, Y., Izumi, K., Tsuruo, T., Tanaka, T., Miyasaka, M., and Sone, S. 1996. Novel metastasis model of human lung cancer in SCID mice depleted of NK cells. Int. J. Cancer 67: 211–217.
Young, M.R. and Newby, M. 1986. Differential induction of suppressor macrophages by cloned lewis lung carcinoma variants in mice. J. Natl. Cancer Inst. 77: 1255–1260.
Henry, N., Van Lamsweerde, A.-L., and Vaes, G. 1983. Collagen degradation by metastatic variants of lewis lung carcinoma: Cooperation between tumor cells and macrophages. Cancer Res. 43: 5321–5327.
Gorelik, E., Wiltrout, R.H., Brunda, M.J., Holden, H.T., andHerberman, R.B. 1982. Augmentation of metastasis formation by thioglycollate-elicited macrophages. Int. J. Cancer 29: 575–581.
Duffie, G.P. and Young, M.R. 1991. Tumoricidal activity of alveolar and peritoneal macrophages of C57bl/6 mice bearing metastatic or nonmetastatic variants of lewis lung carcinoma. J. Leukoc. Biol. 49: 8–14.
Luo, Y., Zhou H., Krueger, J., Kaplan, C., Lee, S., Dolman, C., Markowitz, D., Wu, W., Liu, C., Reisfeld, R.A., Xiang, R. 2006. Targeting tumor-associated macrophages as a novel strategy against breast cancer. J. Clin. Invest. 116: 2132–2141.
Chen, J.J.W., Yao, P.-L., Yuan, A., Hong, T.-M., Shun, C.-T., Kuo, M.-L., Lee, Y.-C., and Yang, P.-C. 2003. Up-regulation of tumor interleukin-8 expression by infiltrating macrophages: Its correlation with tumor angiogenesis and patient survival in non-small cell lung cancer. Clin. Cancer Res. 9: 729–737.
Cornelius, L.A., Nehring, L.C., Harding, E., Bolanowski, M., Welgus, H.G., Kobayashi, D.K., Pierce, R.A., and Shapiro, S.D. 1998. Matrix metalloproteinases generate angiostatin: Effects on neovascularization. J. Immunol. 161: 6845–6852.
Dong, Z., Kumar, R., Yang, X., and Fidler, I.J. 1997. Macrophage-derived metalloelastase is responsible for the generation of angiostatin in lewis lung carcinoma. Cell 88: 801–810.
Montuenga, L.M. and Pio, R. 2007. Tumour-associated macrophages in nonsmall cell lung cancer: The role of interleukin-10. Eur. Respir. J. 30: 608–610.
Sato, T., Takahashi, S., Mizumoto, T., Harao, M., Akizuki, M., Takasugi, M., Fukutomi, T., and Yamashita, J.-I. 2006. Neutrophil elastase and cancer. Surg. Oncol. 15: 217–222.
Bingle, L., Brown, N., and Lewis, C.E. 2002. The role of tumor-associated macrophages in tumor progression: Implications for new anticancer therapies. J. Pathol. 196: 254–265.
Chen, J.J., Lin, Y.C., Yao, P.L., Yuan, A., Chen, H.Y., Shun, C.T., Tsai, M.F., Chen, C.H., and Yang, P.C. 2005. Tumor-associated macrophages: The double-edged sword in cancer progression. J. Clin. Oncol. 23: 953–964.
Takeo, S., Yasumoto, K., Nagashima, A., Nakahashi, H., Sugimachi, K., and Nomoto, K. 1986. Role of tumor-associated macrophages in lung cancer. Cancer Res. 46: 3179–3182.
Johnson, S.K., Kerr, K.M., Chapman, A.D., Kennedy, M.M., King, G., Cockburn, J.S., and Jeffrey, R.R. 1999. Immune cell infiltrates and prognosis in primary carcinoma of the lung. Lung Cancer 27: 27–35.
Toomey, D., Symthe, G., Condron, C., Kelly, J., Byrne, A.M., Kay, E., Conroy, R.M., Broe, P., and Bouchier-Hayes, D. 2003. Infiltrating immune cells, but not tumour cells, express fasl in non-small cell lung cancer: No association with prognosis identified in 3-year follow-up. Intl. J. Cancer 103: 408–412.
Welsh, T.J., Green, R.H., Richardson, D., Waller, D.A., O’byrne, K.J., and Bradding, P. 2005. Macrophage and mast-cell invasion of tumor cell islets confers a marked survival advantage in non-small-cell lung cancer. J. Clin. Oncol. 23: 8959–8967.
Zeni, E., Mazzetti, L., Miotto, D., Lo Cascio, N., Maestrelli, P., Querzoli, P., Pedriali, M., De Rosa, E., Fabbri, L.M., Mapp, C.E., and Boschetto, P. 2007. Macrophage expression of interleukin-10 is a prognostic factor in nonsmall cell lung cancer. Eur. Respir. J. 30: 627–632.
Junker, N., Johansen, J.S., Andersen, C.B., and Kristjansen, P.E.G. 2005. Expression of YKL-40 by peritumoral macrophages in human small cell lung cancer. Lung Cancer 48: 223–231.
Ferrigno, D.B.G. 2003. Hematologic counts and clinical correlates in 1201 newly diagnosed lung cancer patients. Monaldi Arch. Chest Dis. 59: 193–198.
Kerr, K.M., Johnson, S.K., King, G., Kennedy, M.M., Weir, J. and Jeffrey, R. 1998. Partial regression in primary carcinoma of the lung: Does it occur? Histopathology 33:55–63.
Arenberg, D.A., Keane, M.P. Digiovine, B., Kunkle, S.L., Strom, S.R, Burdick, M.D., Iannettoni, M.D., and Strieter, R.M. 2000. Macrophage infiltration in human non-small-cell lung cancer: The role of cc chemokines. Cancer Immunol. Immunother 49:63–70.
Tataroglu, C., Kargi, A., Ozkal, S., Esrefoglu, N., and Akkoclu, A. 2004. Association of macrophages, mast cells and eosinophil leukocytes with angiogenesis and tumor stage in non-small cell lung carcinomas (nsclc). Lung Cancer 43: 47–54.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Fridlender, Z.G., Crisanti, M.C., Albelda, S.M. (2009). The Role of Tumor-Associated Macrophages and Other Innate Immune Cells in Metastatic Progression of Lung Cancer. In: Keshamouni, V., Arenberg, D., Kalemkerian, G. (eds) Lung Cancer Metastasis. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0772-1_11
Download citation
DOI: https://doi.org/10.1007/978-1-4419-0772-1_11
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4419-0771-4
Online ISBN: 978-1-4419-0772-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)