Skip to main content
SpringerLink
Log in

Mechanisms of Immune Evasion by Cancer

  • Chapter
  • First Online:
Immunotherapy of Melanoma

Abstract

Immune system is well developed to recognize foreign organisms invading the host and also the modified/transformed cells of the host such as cancer cells that are harmful for host’s survival. Immunosurveillance , is a process by which immune system monitors the cells/tissues continuously and eliminates the modified or transformed cells. While the immune cells have unique abilities to detect the abnormally dividing cells, tumors also develop specialized mechanisms to avoid immune cell recognition and also to counter the attacks by immune cells. Different types of mechanisms employed by tumor cells to evade an immune attack are discussed in detail in this chapter. The chapter begins with a brief introduction on the significance of immune evasion in cancer prognosis followed by discussion on immunosurveillance with details on the four phases of immunosurveillance Next, the concept of immunoediting is introduced and then the various immune evasive mechanisms employed by cancer cells are discussed including, loss of T-cell recognition caused due to loss of MHC I expression and/or loss of antigen presenting machinery, inhibition of T-cell recruitment to the tumors, intrinsic resistance to apoptosis induced by death receptor pathways, counterattack mechanisms employed by tumor cells, accumulation of immune suppressor cells such as Tregs , MDSCs and TAMs in the tumor microenvironment, targeting metabolic pathways of T-cells by causing amino acid depletion, secretion of immuno-inhibitory cytokines such as TGFβ, MIF as well as PGE2 and most importantly expression of ligands for negative regulatory receptors on T-cells.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Smyth, M. J., Godfrey, D. I., & Trapani, J. A. (2001). A fresh look at tumor immunosurveillance and immunotherapy. Nature Immunology, 2(4), 293–299. doi:10.1038/86297

    Article  CAS  PubMed  Google Scholar 

  2. Igney, F. H., & Krammer, P. H. (2002). Immune escape of tumors: Apoptosis resistance and tumor counterattack. Journal of Leukocyte Biology, 71(6), 907–920.

    CAS  PubMed  Google Scholar 

  3. Dunn, G. P., Old, L. J., & Schreiber, R. D. (2004). The immunobiology of cancer immunosurveillance and immunoediting. Immunity, 21(2), 137–148. doi:10.1016/j.immuni.2004.07.017 S1074761304002092 [pii].

  4. Kim, R., Emi, M., & Tanabe, K. (2007). Cancer immunoediting from immune surveillance to immune escape. Immunology, 121(1), 1–14. doi:10.1111/j.1365-2567.2007.02587.x IMM2587 [pii].

  5. Vinay, D. S., Ryan, E. P., Pawelec, G., Talib, W. H., Stagg, J., Elkord, E., et al. (2015). Immune evasion in cancer: Mechanistic basis and therapeutic strategies. Seminars in Cancer Biology, 35, S185–S198. doi:10.1016/j.semcancer.2015.03.004 S1044-579X(15)00019-X [pii].

  6. Topfer, K., Kempe, S., Muller, N., Schmitz, M., Bachmann, M., Cartellieri, M., et al. (2011). Tumor evasion from T cell surveillance. Journal of Biomedicine and Biotechnology, 2011, 918471. doi:10.1155/2011/918471

    Article  PubMed  PubMed Central  Google Scholar 

  7. Liu, K. (2010). Role of apoptosis resistance in immune evasion and metastasis of colorectal cancer. World Journal of Gastrointestinal Oncology, 2(11), 399–406. doi:10.4251/wjgo.v2.i11.399

    Article  PubMed  PubMed Central  Google Scholar 

  8. Erhlich, P. (1909). Uber den jetzigen Stand der Karzinomforschung. Nederlands Tijdschrift voor Geneeskunde, 5, 273–290.

    Google Scholar 

  9. Weston, B. J. (Ed.). (1973). The thymus and immune surveillance. In: Contemporary topics in immunobiology (Vol. II). Springer US.

    Google Scholar 

  10. Burnet, F. M. (1970). The concept of immunological surveillance. Progress in Experimental Tumor Research, 13, 1–27.

    Article  CAS  PubMed  Google Scholar 

  11. Teng, M. W., Swann, J. B., Koebel, C. M., Schreiber, R. D., & Smyth, M. J. (2008). Immune-mediated dormancy: An equilibrium with cancer. Journal of Leukocyte Biology, 84(4), 988–993. doi:10.1189/jlb.1107774 jlb.1107774 [pii].

  12. Vajdic, C. M., & van Leeuwen, M. T. (2009). Cancer incidence and risk factors after solid organ transplantation. International Journal of Cancer, 125(8), 1747–1754. doi:10.1002/ijc.24439

    Article  CAS  PubMed  Google Scholar 

  13. Vajdic, C. M., van Leeuwen, M. T., & Grulich, A. E. (2009). A role for ageing and HIV infection in HIV-related cancer risk. AIDS, 23(9), 1183–1184. doi:10.1097/QAD.0b013e32832cb284 00002030-200906010-00020 [pii].

  14. Crum-Cianflone, N., Hullsiek, K. H., Marconi, V., Weintrob, A., Ganesan, A., Barthel, R. V., et al. (2009). Trends in the incidence of cancers among HIV-infected persons and the impact of antiretroviral therapy: A 20-year cohort study. AIDS, 23(1), 41–50. doi:10.1097/QAD.0b013e328317cc2d 00002030-200901020-00007 [pii].

  15. Nelson, B. H. (2008). The impact of T-cell immunity on ovarian cancer outcomes. Immunological Reviews, 222, 101–116. doi:10.1111/j.1600-065X.2008.00614.x IMR614 [pii].

  16. Pages, F., Galon, J., Dieu-Nosjean, M. C., Tartour, E., Sautes-Fridman, C., & Fridman, W. H. (2010). Immune infiltration in human tumors: A prognostic factor that should not be ignored. Oncogene, 29(8), 1093–1102. doi:10.1038/onc.2009.416 onc2009416 [pii].

    Google Scholar 

  17. Printz, C. (2001). Spontaneous regression of melanoma may offer insight into cancer immunology. Journal of the National Cancer Institute, 93(14), 1047–1048.

    Article  CAS  PubMed  Google Scholar 

  18. Kalialis, L. V., Drzewiecki, K. T., & Klyver, H. (2009). Spontaneous regression of metastases from melanoma: Review of the literature. Melanoma Research, 19(5), 275–282. doi:10.1097/CMR.0b013e32832eabd5

    Article  PubMed  Google Scholar 

  19. Maio, M. (2012). Melanoma as a model tumour for immuno-oncology. Annals of Oncology, 23(Suppl 8), viii10–viii14. doi:10.1093/annonc/mds257 mds257 [pii].

  20. Dunn, G. P., Bruce, A. T., Ikeda, H., Old, L. J., & Schreiber, R. D. (2002). Cancer immunoediting: From immunosurveillance to tumor escape. Nature Immunology, 3(11), 991–998. doi:10.1038/ni1102-991 ni1102-991 [pii].

  21. Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: The next generation. Cell, 144(5), 646–674. doi:10.1016/j.cell.2011.02.013 S0092-8674(11)00127-9 [pii].

  22. Svane, I. M., Engel, A. M., Nielsen, M. B., Ljunggren, H. G., Rygaard, J., & Werdelin, O. (1996). Chemically induced sarcomas from nude mice are more immunogenic than similar sarcomas from congenic normal mice. European Journal of Immunology, 26(8), 1844–1850. doi:10.1002/eji.1830260827

    Article  CAS  PubMed  Google Scholar 

  23. Engel, A. M., Svane, I. M., Rygaard, J., & Werdelin, O. (1997). MCA sarcomas induced in scid mice are more immunogenic than MCA sarcomas induced in congenic, immunocompetent mice. Scandinavian Journal of Immunology, 45(5), 463–470.

    Article  CAS  PubMed  Google Scholar 

  24. Shankaran, V., Ikeda, H., Bruce, A. T., White, J. M., Swanson, P. E., Old, L. J., et al. (2001). IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature, 410(6832), 1107–1111. doi:10.1038/35074122 35074122 [pii].

  25. MacKie, R. M., Reid, R., & Junor, B. (2003). Fatal melanoma transferred in a donated kidney 16 years after melanoma surgery. New England Journal of Medicine, 348(6), 567–568. doi:10.1056/NEJM200302063480620 348/6/567 [pii].

  26. Kim, U., Baumler, A., Carruthers, C., & Bielat, K. (1975). Immunological escape mechanism in spontaneously metastasizing mammary tumors. Proceedings of the National Academy of Sciences, 72(3), 1012–1016.

    Article  CAS  Google Scholar 

  27. Stackpole, C. W., Cremona, P., Leonard, C., & Stremmel, P. (1980). Antigenic modulation as a mechanism for tumor escape from immune destruction: Identification of modulation-positive and modulation-negative mouse lymphomas with xenoantisera to murine leukemia virus gp70. The Journal of Immunology, 125(4), 1715–1723.

    CAS  PubMed  Google Scholar 

  28. Vasmel, W. L., Sijts, E. J., Leupers, C. J., Matthews, E. A., & Melief, C. J. (1989). Primary virus-induced lymphomas evade T cell immunity by failure to express viral antigens. Journal of Experimental Medicine, 169(4), 1233–1254.

    Article  CAS  PubMed  Google Scholar 

  29. Maeurer, M. J., Gollin, S. M., Martin, D., Swaney, W., Bryant, J., Castelli, C., et al. (1996). Tumor escape from immune recognition: Lethal recurrent melanoma in a patient associated with downregulation of the peptide transporter protein TAP-1 and loss of expression of the immunodominant MART-1/Melan-A antigen. Journal of Clinical Investigation, 98(7), 1633–1641. doi:10.1172/JCI118958

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Meissner, M., Reichert, T. E., Kunkel, M., Gooding, W., Whiteside, T. L., Ferrone, S., et al. (2005). Defects in the human leukocyte antigen class I antigen processing machinery in head and neck squamous cell carcinoma: Association with clinical outcome. Clinical Cancer Research, 11(7), 2552–2560, doi:10.1158/1078-0432.CCR-04-2146 11/7/2552 [pii].

  31. Nie, Y., Yang, G., Song, Y., Zhao, X., So, C., Liao, J., et al. (2001). DNA hypermethylation is a mechanism for loss of expression of the HLA class I genes in human esophageal squamous cell carcinomas. Carcinogenesis, 22(10), 1615–1623.

    Article  CAS  PubMed  Google Scholar 

  32. Korkolopoulou, P., Kaklamanis, L., Pezzella, F., Harris, A. L., & Gatter, K. C. (1996). Loss of antigen-presenting molecules (MHC class I and TAP-1) in lung cancer. British Journal of Cancer, 73(2), 148–153.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Sanda, M. G., Restifo, N. P., Walsh, J. C., Kawakami, Y., Nelson, W. G., Pardoll, D. M., et al. (1995). Molecular characterization of defective antigen processing in human prostate cancer. Journal of the National Cancer Institute, 87(4), 280–285.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Serrano, A., Tanzarella, S., Lionello, I., Mendez, R., Traversari, C., Ruiz-Cabello, F., et al. (2001). Rexpression of HLA class I antigens and restoration of antigen-specific CTL response in melanoma cells following 5-aza-2′-deoxycytidine treatment. International Journal of Cancer, 94(2), 243–251. doi:10.1002/ijc.1452 [pii].

  35. Maleno, I., Cabrera, C. M., Cabrera, T., Paco, L., Lopez-Nevot, M. A., Collado, A., et al. (2004). Distribution of HLA class I altered phenotypes in colorectal carcinomas: High frequency of HLA haplotype loss associated with loss of heterozygosity in chromosome region 6p21. Immunogenetics, 56(4), 244–253. doi:10.1007/s00251-004-0692-z

    Article  CAS  PubMed  Google Scholar 

  36. Maleno, I., Romero, J. M., Cabrera, T., Paco, L., Aptsiauri, N., Cozar, J. M., et al. (2006). LOH at 6p21.3 region and HLA class I altered phenotypes in bladder carcinomas. Immunogenetics, 58(7), 503–510. doi:10.1007/s00251-006-0111-8

    Article  CAS  PubMed  Google Scholar 

  37. Bicknell, D. C., Rowan, A., & Bodmer, W. F. (1994). Beta 2-microglobulin gene mutations: A study of established colorectal cell lines and fresh tumors. Proceedings of the National Academy Science United States of America, 91(11), 4751–4755.

    Article  CAS  Google Scholar 

  38. Hicklin, D. J., Wang, Z., Arienti, F., Rivoltini, L., Parmiani, G., & Ferrone, S. (1998). beta2-Microglobulin mutations, HLA class I antigen loss, and tumor progression in melanoma. Journal of Clinical Investigation, 101(12), 2720–2729. doi:10.1172/JCI498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Seliger, B. (2008). Molecular mechanisms of MHC class I abnormalities and APM components in human tumors. Cancer Immunology, Immunotherapy, 57(11), 1719–1726. doi:10.1007/s00262-008-0515-4

    Article  CAS  PubMed  Google Scholar 

  40. Restifo, N. P., Esquivel, F., Kawakami, Y., Yewdell, J. W., Mule, J. J., Rosenberg, S. A., et al. (1993). Identification of human cancers deficient in antigen processing. Journal of Experimental Medicine, 177(2), 265–272.

    Article  CAS  PubMed  Google Scholar 

  41. Manning, J., Indrova, M., Lubyova, B., Pribylova, H., Bieblova, J., Hejnar, J., et al. (2008). Induction of MHC class I molecule cell surface expression and epigenetic activation of antigen-processing machinery components in a murine model for human papilloma virus 16-associated tumours. Immunology, 123(2), 218–227. doi:10.1111/j.1365-2567.2007.02689.x IMM2689 [pii].

  42. White, L. C., Wright, K. L., Felix, N. J., Ruffner, H., Reis, L. F., Pine, R., et al. (1996). Regulation of LMP2 and TAP1 genes by IRF-1 explains the paucity of CD8+ T cells in IRF-1-/- mice. Immunity, 5(4), 365–376. S1074-7613(00)80262-9 [pii].

    Google Scholar 

  43. Rodriguez, T., Mendez, R., Del Campo, A., Jimenez, P., Aptsiauri, N., Garrido, F., et al. (2007). Distinct mechanisms of loss of IFN-gamma mediated HLA class I inducibility in two melanoma cell lines. BMC Cancer, 7, 34. doi:10.1186/1471-2407-7-34 1471-2407-7-34 [pii].

  44. Middleton, J., Patterson, A. M., Gardner, L., Schmutz, C., & Ashton, B. A. (2002). Leukocyte extravasation: Chemokine transport and presentation by the endothelium. Blood, 100(12), 3853–3860. doi:10.1182/blood.V100.12.3853 100/12/3853 [pii].

  45. Strell, C., & Entschladen, F. (2008). Extravasation of leukocytes in comparison to tumor cells. Cell Communication and Signaling, 6, 10. doi:10.1186/1478-811X-6-10 1478-811X-6-10 [pii].

  46. Piali, L., Fichtel, A., Terpe, H. J., Imhof, B. A., & Gisler, R. H. (1995). Endothelial vascular cell adhesion molecule 1 expression is suppressed by melanoma and carcinoma. Journal of Experimental Medicine, 181(2), 811–816.

    Article  CAS  PubMed  Google Scholar 

  47. Madhavan, M., Srinivas, P., Abraham, E., Ahmed, I., Vijayalekshmi, N. R., & Balaram, P. (2002). Down regulation of endothelial adhesion molecules in node positive breast cancer: Possible failure of host defence mechanism. Pathology Oncology Research, 8(2), 125–128. PAOR.2002.8.2.0125

    Google Scholar 

  48. Weishaupt, C., Munoz, K. N., Buzney, E., Kupper, T. S., & Fuhlbrigge, R. C. (2007). T-cell distribution and adhesion receptor expression in metastatic melanoma. Clinical Cancer Research, 13(9), 2549–2556. doi:10.1158/1078-0432.CCR-06-2450 13/9/2549 [pii].

  49. Clark, R. A., Huang, S. J., Murphy, G. F., Mollet, I. G., Hijnen, D., Muthukuru, M., et al. (2008). Human squamous cell carcinomas evade the immune response by down-regulation of vascular E-selectin and recruitment of regulatory T cells. The Journal of Experimental Medicine, 205(10), 2221–2234. doi:10.1084/jem.20071190 jem.20071190 [pii].

  50. Pitti, R. M., Marsters, S. A., Lawrence, D. A., Roy, M., Kischkel, F. C., Dowd, P., et al. (1998). Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Nature, 396(6712), 699–703. doi:10.1038/25387

    Article  CAS  PubMed  Google Scholar 

  51. Cheng, J., Zhou, T., Liu, C., Shapiro, J. P., Brauer, M. J., Kiefer, M. C., et al. (1994). Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule. Science, 263(5154), 1759–1762.

    Article  CAS  PubMed  Google Scholar 

  52. Midis, G. P., Shen, Y., & Owen-Schaub, L. B. (1996). Elevated soluble Fas (sFas) levels in nonhematopoietic human malignancy. Cancer Research, 56(17), 3870–3874.

    CAS  PubMed  Google Scholar 

  53. Ugurel, S., Rappl, G., Tilgen, W., & Reinhold, U. (2001). Increased soluble CD95 (sFas/CD95) serum level correlates with poor prognosis in melanoma patients. Clinical Cancer Research, 7(5), 1282–1286.

    CAS  PubMed  Google Scholar 

  54. Roth, W., Isenmann, S., Nakamura, M., Platten, M., Wick, W., Kleihues, P., et al. (2001). Soluble decoy receptor 3 is expressed by malignant gliomas and suppresses CD95 ligand-induced apoptosis and chemotaxis. Cancer Research, 61(6), 2759–2765.

    CAS  PubMed  Google Scholar 

  55. Sheikh, M. S., Huang, Y., Fernandez-Salas, E. A., El-Deiry, W. S., Friess, H., Amundson, S., et al. (1999). The antiapoptotic decoy receptor TRID/TRAIL-R3 is a p53-regulated DNA damage-inducible gene that is overexpressed in primary tumors of the gastrointestinal tract. Oncogene, 18(28), 4153–4159. doi:10.1038/sj.onc.1202763

    Article  CAS  PubMed  Google Scholar 

  56. Meng, R. D., McDonald, E. R., 3rd, Sheikh, M. S., Fornace, A. J., Jr., & El-Deiry, W. S. (2000). The TRAIL decoy receptor TRUNDD (DcR2, TRAIL-R4) is induced by adenovirus-p 53 overexpression and can delay TRAIL-, p53-, and KILLER/DR5-dependent colon cancer apoptosis. Molecular Therapy, 1(2), 130–144. doi:10.1006/mthe.2000.0025 S1525-0016(00)90025-X [pii].

  57. Krueger, A., Baumann, S., Krammer, P. H., & Kirchhoff, S. (2001). FLICE-inhibitory proteins: regulators of death receptor-mediated apoptosis. Molecular and Cellular Biology, 21(24), 8247–8254. doi:10.1128/MCB.21.24.8247-8254.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Nam, S. Y., Jung, G. A., Hur, G. C., Chung, H. Y., Kim, W. H., Seol, D. W., et al. (2003). Upregulation of FLIP(S) by Akt, a possible inhibition mechanism of TRAIL-induced apoptosis in human gastric cancers. Cancer Science, 94(12), 1066–1073.

    Article  CAS  PubMed  Google Scholar 

  59. Xiao, C. W., Yan, X., Li, Y., Reddy, S. A., & Tsang, B. K. (2003). Resistance of human ovarian cancer cells to tumor necrosis factor alpha is a consequence of nuclear factor kappaB-mediated induction of Fas-associated death domain-like interleukin-1beta-converting enzyme-like inhibitory protein. Endocrinology, 144(2), 623–630. doi:10.1210/en.2001-211024

    Article  CAS  PubMed  Google Scholar 

  60. Zhang, X., Jin, T. G., Yang, H., DeWolf, W. C., Khosravi-Far, R., & Olumi, A. F. (2004). Persistent c-FLIP(L) expression is necessary and sufficient to maintain resistance to tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in prostate cancer. Cancer Research, 64(19), 7086–7091. doi:10.1158/0008-5472.CAN-04-1498 64/19/7086 [pii].

  61. Ullenhag, G. J., Mukherjee, A., Watson, N. F., Al-Attar, A. H., Scholefield, J. H., & Durrant, L. G. (2007). Overexpression of FLIPL is an independent marker of poor prognosis in colorectal cancer patients. Clinical Cancer Research, 13(17), 5070–5075. doi:10.1158/1078-0432.CCR-06-2547 13/17/5070 [pii].

  62. Rao-Bindal, K., Rao, C. K., Yu, L., & Kleinerman, E. S. (2013). Expression of c-FLIP in pulmonary metastases in osteosarcoma patients and human xenografts. Pediatric Blood & Cancer, 60(4), 575–579. doi:10.1002/pbc.24412

    Article  Google Scholar 

  63. Ili, C. G., Brebi, P., Tapia, O., Sandoval, A., Lopez, J., Garcia, P., et al. (2013). Cellular FLICE-like inhibitory protein long form (c-FLIPL) overexpression is related to cervical cancer progression. International Journal of Gynecological Pathology, 32(3), 316–322. doi:10.1097/PGP.0b013e31825d8064

    Article  CAS  PubMed  Google Scholar 

  64. McLornan, D., Hay, J., McLaughlin, K., Holohan, C., Burnett, A. K., Hills, R. K., et al. (2013). Prognostic and therapeutic relevance of c-FLIP in acute myeloid leukaemia. British Journal of Haematology, 160(2), 188–198. doi:10.1111/bjh.12108

    Article  CAS  PubMed  Google Scholar 

  65. Lee, S. W., Cho, J. M., Cho, H. J., Kang, J. Y., Kim, E. K., & Yoo, T. K. (2015). Expression levels of heat shock protein 27 and cellular FLICE-like inhibitory protein in prostate cancer correlate with Gleason score sum and pathologic stage. Korean Journal of Urology, 56(7), 505–514. doi:10.4111/kju.2015.56.7.505

    Article  PubMed  PubMed Central  Google Scholar 

  66. Yao, Q., Du, J., Lin, J., Luo, Y., Wang, Y., Liu, Y., et al. (2016). Prognostic significance of TRAIL signalling molecules in cervical squamous cell carcinoma. Journal of Clinical Pathology, 69(2), 122–127. doi:10.1136/jclinpath-2014-202811 jclinpath-2014-202811 [pii].

  67. Safa, A. R., & Pollok, K. E. (2011). Targeting the anti-apoptotic protein c-FLIP for cancer therapy. Cancers (Basel), 3(2), 1639–1671. doi:10.3390/cancers3021639

    Article  CAS  Google Scholar 

  68. Landowski, T. H., Qu, N., Buyuksal, I., Painter, J. S., & Dalton, W. S. (1997). Mutations in the Fas antigen in patients with multiple myeloma. Blood, 90(11), 4266–4270.

    CAS  PubMed  Google Scholar 

  69. Maeda, T., Yamada, Y., Moriuchi, R., Sugahara, K., Tsuruda, K., Joh, T., et al. (1999). Fas gene mutation in the progression of adult T cell leukemia. Journal of Experimental Medicine, 189(7), 1063–1071.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Park, W. S., Oh, R. R., Kim, Y. S., Park, J. Y., Lee, S. H., Shin, M. S., et al. (2001). Somatic mutations in the death domain of the Fas (Apo-1/CD95) gene in gastric cancer. The Journal of Pathology, 193(2), 162–168. doi:10.1002/1096-9896(2000)9999:9999<::AID-PATH759>3.0.CO;2-A [pii].

  71. Shin, M. S., Kim, H. S., Lee, S. H., Park, W. S., Kim, S. Y., Park, J. Y., et al. (2001). Mutations of tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) and receptor 2 (TRAIL-R2) genes in metastatic breast cancers. Cancer Research, 61(13), 4942–4946.

    CAS  PubMed  Google Scholar 

  72. Medema, J. P., de Jong, J., Peltenburg, L. T., Verdegaal, E. M., Gorter, A., Bres, S. A., et al. (2001). Blockade of the granzyme B/perforin pathway through overexpression of the serine protease inhibitor PI-9/SPI-6 constitutes a mechanism for immune escape by tumors. Proceedings of the National Academy of Sciences, 98(20), 11515–11520. doi:10.1073/pnas.201398198 201398198 [pii].

  73. van Houdt, I. S., Oudejans, J. J., van den Eertwegh, A. J., Baars, A., Vos, W., Bladergroen, B. A., et al. (2005). Expression of the apoptosis inhibitor protease inhibitor 9 predicts clinical outcome in vaccinated patients with stage III and IV melanoma. Clinical Cancer Research, 11(17), 6400–6407. doi:10.1158/1078-0432.CCR-05-0306 11/17/6400 [pii].

  74. Hahne, M., Rimoldi, D., Schroter, M., Romero, P., Schreier, M., French, L. E., et al. (1996). Melanoma cell expression of Fas(Apo-1/CD95) ligand: Implications for tumor immune escape. Science, 274(5291), 1363–1366.

    Article  CAS  PubMed  Google Scholar 

  75. Niehans, G. A., Brunner, T., Frizelle, S. P., Liston, J. C., Salerno, C. T., Knapp, D. J., et al. (1997). Human lung carcinomas express Fas ligand. Cancer Research, 57(6), 1007–1012.

    CAS  PubMed  Google Scholar 

  76. Mullauer, L., Mosberger, I., Grusch, M., Rudas, M., & Chott, A. (2000). Fas ligand is expressed in normal breast epithelial cells and is frequently up-regulated in breast cancer. The Journal of Pathology, 190(1), 20–30. doi:10.1002/(SICI)1096-9896(200001)190:1<20::AID-PATH497>3.0.CO;2-S [pii].

  77. Bernstorff, W. V., Glickman, J. N., Odze, R. D., Farraye, F. A., Joo, H. G., Goedegebuure, P. S., et al. (2002). Fas (CD95/APO-1) and Fas ligand expression in normal pancreas and pancreatic tumors. Implications for immune privilege and immune escape. Cancer, 94(10), 2552–2560.

    Article  PubMed  Google Scholar 

  78. Maffei, F., Forti, G. C., Castelli, E., Stefanini, G. F., Mattioli, S., & Hrelia, P. (2002). Biomarkers to assess the genetic damage induced by alcohol abuse in human lymphocytes. Mutation Research, 514(1–2), 49–58. S1383571801003187 [pii].

    Google Scholar 

  79. Iero, M., Valenti, R., Huber, V., Filipazzi, P., Parmiani, G., Fais, S., et al. (2008). Tumour-released exosomes and their implications in cancer immunity. Cell Death & Differentiation, 15(1), 80–88. doi:10.1038/sj.cdd.4402237 4402237 [pii].

  80. Motz, G. T., Santoro, S. P., Wang, L. P., Garrabrant, T., Lastra, R. R., Hagemann, I. S., et al. (2014). Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors. Nature Medicine, 20(6), 607–615. doi:10.1038/nm.3541 nm.3541 [pii].

  81. Corthay, A. (2009). How do regulatory T cells work? Scandinavian Journal of Immunology, 70(4), 326–336. doi:10.1111/j.1365-3083.2009.02308.x SJI2308 [pii].

  82. Hiraoka, N., Onozato, K., Kosuge, T., & Hirohashi, S. (2006). Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clinical Cancer Research, 12(18), 5423–5434. doi:10.1158/1078-0432.CCR-06-0369 12/18/5423 [pii].

  83. Curiel, T. J., Coukos, G., Zou, L., Alvarez, X., Cheng, P., Mottram, P., et al. (2004). Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nature Medicine, 10(9), 942–949. doi:10.1038/nm1093nm1093 [pii].

  84. Kobayashi, N., Hiraoka, N., Yamagami, W., Ojima, H., Kanai, Y., Kosuge, T., et al. (2007). FOXP3+ regulatory T cells affect the development and progression of hepatocarcinogenesis. Clinical Cancer Research, 13(3), 902–911. doi:10.1158/1078-0432.CCR-06-2363 13/3/902 [pii].

  85. Viguier, M., Lemaitre, F., Verola, O., Cho, M. S., Gorochov, G., Dubertret, L., et al. (2004). Foxp3 expressing CD4+CD25(high) regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells. The Journal of Immunology, 173(2), 1444–1453.

    Article  CAS  PubMed  Google Scholar 

  86. Gabrilovich, D. I., & Nagaraj, S. (2009). Myeloid-derived suppressor cells as regulators of the immune system. Nature Reviews Immunology, 9(3), 162–174. doi:10.1038/nri2506 nri2506 [pii].

  87. Almand, B., Resser, J. R., Lindman, B., Nadaf, S., Clark, J. I., Kwon, E. D., et al. (2000). Clinical significance of defective dendritic cell differentiation in cancer. Clinical Cancer Research, 6(5), 1755–1766.

    CAS  PubMed  Google Scholar 

  88. Marvel, D., & Gabrilovich, D. I. (2015). Myeloid-derived suppressor cells in the tumor microenvironment: Expect the unexpected. The Journal of Clinical Investigation, 125(9), 3356–3364. doi:10.1172/JCI80005 80005 [pii].

  89. Meyer, C., Cagnon, L., Costa-Nunes, C. M., Baumgaertner, P., Montandon, N., Leyvraz, L., et al. (2014). Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with ipilimumab. Cancer Immunology, Immunotherapy, 63(3), 247–257. doi:10.1007/s00262-013-1508-5

    Article  CAS  PubMed  Google Scholar 

  90. Wang, Z., Zhang, Y., Liu, Y., Wang, L., Zhao, L., Yang, T., et al. (2014). Association of myeloid-derived suppressor cells and efficacy of cytokine-induced killer cell immunotherapy in metastatic renal cell carcinoma patients. Journal of Immunotherapy, 37(1), 43–50. doi:10.1097/CJI.0000000000000005 00002371-201401000-00006 [pii].

  91. Finkelstein, S. E., Carey, T., Fricke, I., Yu, D., Goetz, D., Gratz, M., et al. (2010). Changes in dendritic cell phenotype after a new high-dose weekly schedule of interleukin-2 therapy for kidney cancer and melanoma. Journal of Immunotherapy, 33(8), 817–827. doi:10.1097/CJI.0b013e3181ecccad

    Article  CAS  PubMed  Google Scholar 

  92. Quatromoni, J. G., & Eruslanov, E. (2012). Tumor-associated macrophages: Function, phenotype, and link to prognosis in human lung cancer. American Journal of Translational Research, 4(4), 376–389.

    PubMed  PubMed Central  Google Scholar 

  93. Noy, R., & Pollard, J. W. (2014). Tumor-associated macrophages: From mechanisms to therapy. Immunity, 41(1), 49–61. doi:10.1016/j.immuni.2014.06.010 S1074-7613(14)00230-1 [pii].

  94. Qian, B. Z., & Pollard, J. W. (2010). Macrophage diversity enhances tumor progression and metastasis. Cell, 141(1), 39–51. doi:10.1016/j.cell.2010.03.014 S0092-8674(10)00287-4 [pii].

  95. Bingle, L., Brown, N. J., & Lewis, C. E. (2002). The role of tumour-associated macrophages in tumour progression: Implications for new anticancer therapies. The Journal of Pathology, 196(3), 254–265. doi:10.1002/path.1027 [pii].

  96. Chen, P., Huang, Y., Bong, R., Ding, Y., Song, N., Wang, X., et al. (2011). Tumor-associated macrophages promote angiogenesis and melanoma growth via adrenomedullin in a paracrine and autocrine manner. Clinical Cancer Research, 17(23), 7230–7239. doi:10.1158/1078-0432.CCR-11-1354 1078-0432.CCR-11-1354 [pii].

  97. Hu, W., Qian, Y., Yu, F., Liu, W., Wu, Y., Fang, X., et al. (2015). Alternatively activated macrophages are associated with metastasis and poor prognosis in prostate adenocarcinoma. Oncology Letters, 10(3), 1390–1396. doi:10.3892/ol.2015.3400 OL-0-0-3400 [pii].

  98. Weber, M., Iliopoulos, C., Moebius, P., Buttner-Herold, M., Amann, K., Ries, J., et al. (2016). Prognostic significance of macrophage polarization in early stage oral squamous cell carcinomas. Oral Oncology, 52, 75–84. doi:10.1016/j.oraloncology.2015.11.001 S1368-8375(15)00367-X [pii].

  99. Hung, N. A., Eiholzer, R. A., Kirs, S., Zhou, J., Ward-Hartstonge, K., Wiles, A. K., et al. (2016). Telomere profiles and tumor-associated macrophages with different immune signatures affect prognosis in glioblastoma. Modern Pathology, 29(3), 212–226. doi:10.1038/modpathol.2015.156 modpathol2015156 [pii].

  100. Wang, J., Chen, H., Chen, X., & Lin, H. (2016). Expression of tumor-related macrophages and cytokines after surgery of triple-negative breast cancer patients and its implications. Medical Science Monitor, 22, 115–120. 895386 [pii].

    Google Scholar 

  101. Hu, H., Hang, J. J., Han, T., Zhuo, M., Jiao, F., & Wang, L. W. (2016). The M2 phenotype of tumor-associated macrophages in the stroma confers a poor prognosis in pancreatic cancer. Tumor Biology. doi:10.1007/s13277-015-4741-z [pii].

  102. Zhang, J., Yan, Y., Yang, Y., Wang, L., Li, M., Wang, J., et al. (2016). High infiltration of tumor-associated macrophages influences poor prognosis in human gastric cancer patients, associates with the phenomenon of EMT. Medicine (Baltimore), 95(6), e2636. doi:10.1097/MD.0000000000002636 00005792-201602090-00028 [pii].

  103. Munn, D. H., & Mellor, A. L. (2007). Indoleamine 2,3-dioxygenase and tumor-induced tolerance. The Journal of Clinical Investigation, 117(5), 1147–1154. doi:10.1172/JCI31178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Rodriguez, P. C., & Ochoa, A. C. (2008). Arginine regulation by myeloid derived suppressor cells and tolerance in cancer: Mechanisms and therapeutic perspectives. Immunological Reviews, 222, 180–191. doi:10.1111/j.1600-065X.2008.00608.x IMR608 [pii].

  105. Munn, D. H., Sharma, M. D., Baban, B., Harding, H. P., Zhang, Y., Ron, D., et al. (2005). GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase. Immunity, 22(5), 633–642. doi:10.1016/j.immuni.2005.03.013 S1074-7613(05)00108-1 [pii].

  106. Hwang, S. L., Chung, N. P., Chan, J. K., & Lin, C. L. (2005). Indoleamine 2, 3-dioxygenase (IDO) is essential for dendritic cell activation and chemotactic responsiveness to chemokines. Cell Research, 15(3), 167–175. doi:10.1038/sj.cr.7290282

    Article  CAS  PubMed  Google Scholar 

  107. Uyttenhove, C., Pilotte, L., Theate, I., Stroobant, V., Colau, D., Parmentier, N., et al. (2003). Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nature Medicine, 9(10), 1269–1274. doi:10.1038/nm934nm934 [pii].

  108. Lee, J. R., Dalton, R. R., Messina, J. L., Sharma, M. D., Smith, D. M., Burgess, R. E., et al. (2003). Pattern of recruitment of immunoregulatory antigen-presenting cells in malignant melanoma. Laboratory Investigation, 83(10), 1457–1466.

    Article  CAS  PubMed  Google Scholar 

  109. Prendergast, G. C. (2008). Immune escape as a fundamental trait of cancer: Focus on IDO. Oncogene, 27(28), 3889–3900. doi:10.1038/onc.2008.35 onc200835 [pii].

    Google Scholar 

  110. Ino, K., Tanizaki, Y., Kobayashi, A., Toujima, S., Mabuchi, Y., & Minami, S. (2012). Role of the immune tolerance-inducing molecule indoleamine 2,3-dioxygenase in gynecologic cancers. Journal Cancer Science & Therapy, S13(004). doi:10.4172/1948-5956.S13-001

  111. Chang, C. I., Liao, J. C., & Kuo, L. (2001). Macrophage arginase promotes tumor cell growth and suppresses nitric oxide-mediated tumor cytotoxicity. Cancer Research, 61(3), 1100–1106.

    CAS  PubMed  Google Scholar 

  112. Suer Gokmen, S., Yoruk, Y., Cakir, E., Yorulmaz, F., & Gulen, S. (1999). Arginase and ornithine, as markers in human non-small cell lung carcinoma. Cancer Biochemistry Biophysics, 17(1–2), 125–131.

    CAS  PubMed  Google Scholar 

  113. Singh, R., Pervin, S., Karimi, A., Cederbaum, S., & Chaudhuri, G. (2000). Arginase activity in human breast cancer cell lines: N(omega)-hydroxy-L-arginine selectively inhibits cell proliferation and induces apoptosis in MDA-MB-468 cells. Cancer Research, 60(12), 3305–3312.

    CAS  PubMed  Google Scholar 

  114. Massague, J. (2008). TGFbeta in Cancer. Cell, 134(2). 215–230, doi:10.1016/j.cell.2008.07.001 S0092-8674(08)00878-7 [pii].

  115. Robson, H., Anderson, E., James, R. D., & Schofield, P. F. (1996). Transforming growth factor beta 1 expression in human colorectal tumours: An independent prognostic marker in a subgroup of poor prognosis patients. British Journal of Cancer, 74(5), 753–758.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. von Rahden, B. H., Stein, H. J., Feith, M., Puhringer, F., Theisen, J., Siewert, J. R., et al. (2006). Overexpression of TGF-beta1 in esophageal (Barrett’s) adenocarcinoma is associated with advanced stage of disease and poor prognosis. Molecular Carcinogenesis, 45(10), 786–794. doi:10.1002/mc.20259

    Article  Google Scholar 

  117. Hasegawa, Y., Takanashi, S., Kanehira, Y., Tsushima, T., Imai, T., & Okumura, K. (2001). Transforming growth factor-beta1 level correlates with angiogenesis, tumor progression, and prognosis in patients with nonsmall cell lung carcinoma. Cancer, 91(5), 964–971. doi:10.1002/1097-0142(20010301)91:5<964::AID-CNCR1086>3.0.CO;2-O [pii].

  118. Reed, J. A., McNutt, N. S., Prieto, V. G., & Albino, A. P. (1994). Expression of transforming growth factor-beta 2 in malignant melanoma correlates with the depth of tumor invasion. Implications for tumor progression. American Journal of Pathology, 145(1), 97–104.

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Perrot, C. Y., Javelaud, D., & Mauviel, A. (2013). Insights into the transforming growth factor-beta signaling pathway in cutaneous melanoma. Annals of Dermatology, 25(2), 135–144. doi:10.5021/ad.2013.25.2.135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Bucala, R., & Donnelly, S. C. (2007). Macrophage migration inhibitory factor: A probable link between inflammation and cancer. Immunity, 26(3), 281–285. doi:10.1016/j.immuni.2007.03.005 S1074-7613(07)00184-7 [pii].

  121. Flaster, H., Bernhagen, J., Calandra, T., & Bucala, R. (2007). The macrophage migration inhibitory factor-glucocorticoid dyad: Regulation of inflammation and immunity. Molecular Endocrinology, 21(6), 1267–1280. doi:10.1210/me.2007-0065 me.2007-0065 [pii].

  122. Conroy, H., Mawhinney, L., & Donnelly, S. C. (2010). Inflammation and cancer: Macrophage migration inhibitory factor (MIF)—The potential missing link. QJM, 103(11), 831–836, doi:10.1093/qjmed/hcq148 hcq148 [pii].

  123. Bernhagen, J., Calandra, T., Mitchell, R. A., Martin, S. B., Tracey, K. J., Voelter, W., et al. (1993). MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia. Nature, 365(6448), 756–759. doi:10.1038/365756a0

    Article  CAS  PubMed  Google Scholar 

  124. Zhou, Q., Yan, X., Gershan, J., Orentas, R. J., & Johnson, B. D. (2008). Expression of macrophage migration inhibitory factor by neuroblastoma leads to the inhibition of antitumor T cell reactivity in vivo. The Journal of Immunology, 181(3), 1877–1886. 181/3/1877 [pii].

    Google Scholar 

  125. Simpson, K. D., Templeton, D. J., & Cross, J. V. (2012). Macrophage migration inhibitory factor promotes tumor growth and metastasis by inducing myeloid-derived suppressor cells in the tumor microenvironment. The Journal of Immunology, 189(12), 5533–5540. doi:10.4049/jimmunol.1201161 jimmunol.1201161 [pii].

  126. Bando, H., Matsumoto, G., Bando, M., Muta, M., Ogawa, T., Funata, N., et al. (2002). Expression of macrophage migration inhibitory factor in human breast cancer: Association with nodal spread. Japanese Journal of Cancer Research, 93(4), 389–396.

    Article  CAS  PubMed  Google Scholar 

  127. Meyer-Siegler, K. L., Vera, P. L., Iczkowski, K. A., Bifulco, C., Lee, A., Gregersen, P. K., et al. (2007). Macrophage migration inhibitory factor (MIF) gene polymorphisms are associated with increased prostate cancer incidence. Genes and Immunity, 8(8), 646–652. doi:10.1038/sj.gene.6364427 6364427 [pii].

  128. Yaddanapudi, K., Rendon, B. E., Lamont, G., Kim, E. J., Al Rayyan, N., Richie, J., et al. (2016). MIF is necessary for late-stage melanoma patient MDSC immune suppression and differentiation. Cancer Immunology Research, 4(2), 101–112. doi:10.1158/2326-6066.CIR-15-0070-T 2326-6066.CIR-15-0070-T [pii].

  129. Nakanishi, M., & Rosenberg, D. W. (2013). Multifaceted roles of PGE2 in inflammation and cancer. Semin Immunopathol, 35(2), 123–137. doi:10.1007/s00281-012-0342-8

    Article  CAS  PubMed  Google Scholar 

  130. Greenhough, A., Smartt, H. J., Moore, A. E., Roberts, H. R., Williams, A. C., Paraskeva, C., et al. (2009). The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis, 30(3), 377–386. doi:10.1093/carcin/bgp014 bgp014 [pii].

  131. Pietra, G., Manzini, C., Rivara, S., Vitale, M., Cantoni, C., Petretto, A., et al. (2012). Melanoma cells inhibit natural killer cell function by modulating the expression of activating receptors and cytolytic activity. Cancer Research, 72(6), 1407–1415. doi:10.1158/0008-5472.CAN-11-2544 0008-5472.CAN-11-2544 [pii].

  132. Pockaj, B. A., Basu, G. D., Pathangey, L. B., Gray, R. J., Hernandez, J. L., Gendler, S. J., et al. (2004). Reduced T-cell and dendritic cell function is related to cyclooxygenase-2 overexpression and prostaglandin E2 secretion in patients with breast cancer. Annals of Surgical Oncology, 11(3), 328–339.

    Article  PubMed  Google Scholar 

  133. Liu, L., Ge, D., Ma, L., Mei, J., Liu, S., Zhang, Q., et al. (2012). Interleukin-17 and prostaglandin E2 are involved in formation of an M2 macrophage-dominant microenvironment in lung cancer. Journal of Thoracic Oncology, 7(7), 1091–1100. doi:10.1097/JTO.0b013e3182542752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Pardoll, D. M. (2012). The blockade of immune checkpoints in cancer immunotherapy. Nature Reviews Cancer, 12(4), 252–264. doi:10.1038/nrc3239 nrc3239 [pii].

  135. Zou, W., & Chen, L. (2008). Inhibitory B7-family molecules in the tumour microenvironment. Nature Reviews Immunology, 8(6), 467–477. doi:10.1038/nri2326 nri2326 [pii].

  136. Salama, A. K., & Hodi, F. S. (2011). Cytotoxic T-lymphocyte-associated antigen-4. Clinical Cancer Research, 17(14), 4622–4628. doi:10.1158/1078-0432.CCR-10-2232 1078-0432.CCR-10-2232 [pii].

  137. Antczak, A., Pastuszak-Lewandoska, D., Gorski, P., Domanska, D., Migdalska-Sek, M., Czarnecka, K., et al. (2013). Ctla-4 expression and polymorphisms in lung tissue of patients with diagnosed non-small-cell lung cancer. Biomed Res Int, 2013, 576486. doi:10.1155/2013/576486

    Article  PubMed  PubMed Central  Google Scholar 

  138. Yu, H., Yang, J., Jiao, S., Li, Y., Zhang, W., & Wang, J. (2015). Cytotoxic T lymphocyte antigen 4 expression in human breast cancer: Implications for prognosis. Cancer Immunology, Immunotherapy, 64(7), 853–860. doi:10.1007/s00262-015-1696-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Deng, L., Gyorffy, B., Na, F., Chen, B., Lan, J., Xue, J., et al. (2015). Association of PDCD1 and CTLA-4 gene expression with clinicopathological factors and survival in non-small-cell lung cancer: Results from a large and pooled microarray database. Journal of Thoracic Oncology, 10(7), 1020–1026. doi:10.1097/JTO.0000000000000550 S1556-0864(15)33489-4 [pii].

  140. Hamanishi, J., Mandai, M., Iwasaki, M., Okazaki, T., Tanaka, Y., Yamaguchi, K., et al. (2007). Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proceedings of the National Academy of Sciences USA, 104(9), 3360–3365. doi:10.1073/pnas.0611533104 0611533104 [pii].

  141. Nakanishi, J., Wada, Y., Matsumoto, K., Azuma, M., Kikuchi, K., & Ueda, S. (2007). Overexpression of B7-H1 (PD-L1) significantly associates with tumor grade and postoperative prognosis in human urothelial cancers. Cancer Immunology, Immunotherapy, 56(8), 1173–1182. doi:10.1007/s00262-006-0266-z

    Article  CAS  PubMed  Google Scholar 

  142. Gadiot, J., Hooijkaas, A. I., Kaiser, A. D., van Tinteren, H., van Boven, H., & Blank, C. (2011). Overall survival and PD-L1 expression in metastasized malignant melanoma. Cancer, 117(10), 2192–2201. doi:10.1002/cncr.25747

    Article  CAS  PubMed  Google Scholar 

  143. Frigola, X., Inman, B. A., Lohse, C. M., Krco, C. J., Cheville, J. C., Thompson, R. H., et al. (2011). Identification of a soluble form of B7-H1 that retains immunosuppressive activity and is associated with aggressive renal cell carcinoma. Clinical Cancer Research, 17(7), 1915–1923. doi:10.1158/1078-0432.CCR-10-0250 1078-0432.CCR-10-0250 [pii].

  144. Ilarregui, J. M., Bianco, G. A., Toscano, M. A., & Rabinovich, G. A. (2005). The coming of age of galectins as immunomodulatory agents: impact of these carbohydrate binding proteins in T cell physiology and chronic inflammatory disorders. Annals of the Rheumatic Diseases, 64(Suppl 4), iv96-103. doi:10.1136/ard.2005.044347 64/suppl_4/iv96 [pii].

  145. Liu, F. T., & Rabinovich, G. A. (2005). Galectins as modulators of tumour progression. Nature Reviews Cancer, 5(1), 29–41. doi:10.1038/nrc1527 nrc1527 [pii].

  146. Cummings, R. D., & Liu, F. T. (2009). Galectins. NBK1944 [bookaccession].

    Google Scholar 

  147. Cindolo, L., Benvenuto, G., Salvatore, P., Pero, R., Salvatore, G., Mirone, V., et al. (1999). Galectin-1 and galectin-3 expression in human bladder transitional-cell carcinomas. International Journal of Cancer, 84(1), 39–43. doi:10.1002/(SICI)1097-0215(19990219)84:1<39::AID-IJC8>3.0.CO;2-E [pii].

  148. Rorive, S., Belot, N., Decaestecker, C., Lefranc, F., Gordower, L., Micik, S., et al. (2001). Galectin-1 is highly expressed in human gliomas with relevance for modulation of invasion of tumor astrocytes into the brain parenchyma. Glia, 33(3), 241–255. doi:10.1002/1098-1136(200103)33:3<241::AID-GLIA1023>3.0.CO;2-1 [pii].

  149. van den Brule, F. A., Waltregny, D., & Castronovo, V. (2001). Increased expression of galectin-1 in carcinoma-associated stroma predicts poor outcome in prostate carcinoma patients. The Journal of Pathology, 193(1), 80–87. doi:10.1002/1096-9896(2000)9999:9999<::AID-PATH730>3.0.CO;2-2 [pii].

  150. van den Brule, F., Califice, S., Garnier, F., Fernandez, P. L., Berchuck, A., & Castronovo, V. (2003). Galectin-1 accumulation in the ovary carcinoma peritumoral stroma is induced by ovary carcinoma cells and affects both cancer cell proliferation and adhesion to laminin-1 and fibronectin. Laboratory Investigation, 83(3), 377–386.

    Article  PubMed  Google Scholar 

  151. Mourad-Zeidan, A. A., Melnikova, V. O., Wang, H., Raz, A., & Bar-Eli, M. (2008). Expression profiling of galectin-3-depleted melanoma cells reveals its major role in melanoma cell plasticity and vasculogenic mimicry. The American Journal of Pathology, 173(6), 1839–1852. doi:10.2353/ajpath.2008.080380 S0002-9440(10)61567-2 [pii].

  152. Ebrahim, A. H., Alalawi, Z., Mirandola, L., Rakhshanda, R., Dahlbeck, S., Nguyen, D., et al. (2014). Galectins in cancer: Carcinogenesis, diagnosis and therapy. Annals of Translation Medicine, 2(9), 88. doi:10.3978/j.issn.2305-5839.2014.09.12 atm-02-09-88 [pii].

Download references

Author information

Authors and Affiliations

  1. Faculty of Medicine, Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada

    Anand Rotte & Madhuri Bhandaru

Authors
  1. Anand Rotte
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Madhuri Bhandaru
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anand Rotte .

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing AG

About this chapter

Cite this chapter

Rotte, A., Bhandaru, M. (2016). Mechanisms of Immune Evasion by Cancer. In: Immunotherapy of Melanoma. Springer, Cham. https://doi.org/10.1007/978-3-319-48066-4_8

Download citation

Publish with us

Policies and ethics

Search

Navigation