Skip to main content
SpringerLink
Log in

Cancer-Induced Signaling Defects in Antitumor T Cells

  • Chapter
Tumor-Induced Immune Suppression

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 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.00
Price excludes VAT (USA)
  • Compact, lightweight 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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abrahamsen, H., Baillie, G., Ngai, J., et al. (2004). TCR- and CD28-mediated recruitment of phosphodiesterase 4 to lipid rafts potentiates TCR signaling. J Immunol 173:4847–4858.

    PubMed  CAS  Google Scholar 

  • Alarcon, B., Gil, D., Delgado, P., and Schamel, W. W. (2003). Initiation of TCR signaling: regulation within CD3 dimers. Immunol Rev 191:38–46.

    PubMed  CAS  Google Scholar 

  • Alexander, J. P., Kudoh, S., Melsop, K. A., et al. (1993). T-cells infiltrating renal cell carcinoma display a poor proliferative response even though they can produce interleukin 2 and express interleukin 2 receptors. Cancer Res 53:1380–1387.

    PubMed  CAS  Google Scholar 

  • Bennaceur, K., Popa, I., Portoukalian, J., Berthier-Vergnes, O., and Peguet-Navarro, J. (2006). Melanoma-derived gangliosides impair migratory and antigen-presenting function of human epidermal Langerhans cells and induce their apoptosis. Int Immunol 18: 879–886.

    PubMed  CAS  Google Scholar 

  • Bergman, M., Mustelin, T., Oetken, C., et al. (1992). The human p50csk tyrosine kinase phosphorylates p56lck at Tyr-505 and down regulates its catalytic activity. EMBO J 11: 2919–2924.

    PubMed  CAS  Google Scholar 

  • Bharti, A. C., and Singh, S. M. (2001). Gangliosides derived from a T cell lymphoma inhibit bone marrow cell proliferation and differentiation. Int Immunopharmacol 1:155–165.

    PubMed  CAS  Google Scholar 

  • Bharti, A. C., and Singh, S. M. (2003). Inhibition of macrophage nitric oxide production by gangliosides derived from a spontaneous T cell lymphoma: the involved mechanisms. Nitric Oxide 8:75–82.

    PubMed  CAS  Google Scholar 

  • Birkeland, M. L., Johnson, P., Trowbridge, I. S., and Pure, E. (1989). Changes in CD45 isoform expression accompany antigen-induced murine T-cell activation. Proc Natl Acad Sci USA 86:6734–6738.

    PubMed  CAS  Google Scholar 

  • Biswas, K., Richmond, A., Rayman, P., et al. (2006). GM2 expression in renal cell carcinoma: potential role in tumor-induced T-cell dysfunction. Cancer Res 66:6816–6825.

    PubMed  CAS  Google Scholar 

  • Blackhall, F. H., and Shepherd, F. A. (2007). Small cell lung cancer and targeted therapies. Curr Opin Oncol 19:103–108.

    PubMed  Google Scholar 

  • Blasioli, J., Paust, S., and Thomas, M. L. (1999). Definition of the sites of interaction between the protein tyrosine phosphatase SHP-1 and CD22. J Biol Chem 274:2303–2307.

    PubMed  CAS  Google Scholar 

  • Boon, T., and Van Pel, A. (1989). T cell-recognized antigenic peptides derived from the cellular genome are not protein degradation products but can be generated directly by transcription and translation of short subgenic regions. A hypothesis. Immunogenetics 29:75–79.

    PubMed  CAS  Google Scholar 

  • Brdicka, T., Pavlistova, D., Leo, A., et al. (2000). Phosphoprotein associated with glycosphingolipid-enriched microdomains (PAG), a novel ubiquitously expressed transmembrane adaptor protein, binds the protein tyrosine kinase csk and is involved in regulation of T cell activation. J Exp Med 191:1591–1604.

    PubMed  CAS  Google Scholar 

  • Brdickova, N., Brdicka, T., Angelisova, P., et al. (2003). LIME: a new membrane Raft-associated adaptor protein involved in CD4 and CD8 coreceptor signaling. J Exp Med 198: 1453–1462.

    PubMed  CAS  Google Scholar 

  • Bronte, V., Cingarlini, S., Marigo, I., et al. (2006). Leukocyte infiltration in cancer creates an unfavorable environment for antitumor immune responses: a novel target for therapeutic intervention. Immunol Invest 35:327–357.

    PubMed  CAS  Google Scholar 

  • Bronte, V., Kasic, T., Gri, G., et al. (2005). Boosting antitumor responses of T lymphocytes infiltrating human prostate cancers. J Exp Med 201:1257–1268.

    PubMed  CAS  Google Scholar 

  • Brumell, J. H., Burkhardt, A. L., Bolen, J. B., and Grinstein, S. (1996). Endogenous reactive oxygen intermediates activate tyrosine kinases in human neutrophils. J Biol Chem 271: 1455–1461.

    PubMed  CAS  Google Scholar 

  • Bukowski, R. M., Rayman, P., Uzzo, R., et al. (1998). Signal transduction abnormalities in T lymphocytes from patients with advanced renal carcinoma: clinical relevance and effects of cytokine therapy. Clin Cancer Res 4:2337–2347.

    PubMed  CAS  Google Scholar 

  • Cardi, G., Heaney, J. A., Schned, A. R., Phillips, D. M., Branda, M. T., and Ernstoff, M. S. (1997). T-cell receptor zeta-chain expression on tumor-infiltrating lymphocytes from renal cell carcinoma. Cancer Res 57:3517–3519.

    PubMed  CAS  Google Scholar 

  • Cherukuri, A., Dykstra, M., and Pierce, S. K. (2001). Floating the raft hypothesis: lipid rafts play a role in immune cell activation. Immunity 14:657–660.

    PubMed  CAS  Google Scholar 

  • Chiang, G. G., and Sefton, B. M. (2001). Specific dephosphorylation of the Lck tyrosine protein kinase at Tyr-394 by the SHP-1 protein-tyrosine phosphatase. J Biol Chem 276: 23173–23178.

    PubMed  CAS  Google Scholar 

  • Choi, Y. B., Kim, C. K., and Yun, Y. (1999). Lad, an adapter protein interacting with the SH2 domain of p56lck, is required for T cell activation. J Immunol 163:5242–5249.

    PubMed  CAS  Google Scholar 

  • Chung, C. D., Patel, V. P., Moran, M., Lewis, L. A., and Miceli, M. C. (2000). Galectin-1 induces partial TCR zeta-chain phosphorylation and antagonizes processive TCR signal transduction. J Immunol 165:3722–3729.

    PubMed  CAS  Google Scholar 

  • Clements, J. L., Boerth, N. J., Lee, J. R., and Koretzky, G. A. (1999). Integration of T cell receptor-dependent signaling pathways by adapter proteins. Annu Rev Immunol 17:89–108.

    PubMed  CAS  Google Scholar 

  • Cochran, A. J., Huang, R. R., Lee, J., Itakura, E., Leong, S. P., and Essner, R. (2006). Tumour-induced immune modulation of sentinel lymph nodes. Nat Rev Immunol 6:659–670.

    PubMed  CAS  Google Scholar 

  • Correa, M. R., Ochoa, A. C., Ghosh, P., Mizoguchi, H., Harvey, L., and Longo, D. L. (1997). Sequential development of structural and functional alterations in T cells from tumor-bearing mice. J Immunol 158:5292–5296.

    PubMed  CAS  Google Scholar 

  • Coulie, P. G., Lehmann, F., Lethe, B., et al. (1995). A mutated intron sequence codes for an antigenic peptide recognized by cytolytic T lymphocytes on a human melanoma. Proc Natl Acad Sci USA 92:7976–7980.

    PubMed  CAS  Google Scholar 

  • Cuenca, A., Cheng, F., Wang, H., et al. (2003). Extra-lymphatic solid tumor growth is not immunologically ignored and results in early induction of antigen-specific T-cell anergy: dominant role of cross-tolerance to tumor antigens. Cancer Res 63:9007–9015.

    PubMed  CAS  Google Scholar 

  • Curiel, T. J., Coukos, G., Zou, L., et al. (2004). Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10: 942–949.

    PubMed  CAS  Google Scholar 

  • D’Ambrosio, D., Hippen, K. L., Minskoff, S. A., et al. (1995). Recruitment and activation of PTP1C in negative regulation of antigen receptor signaling by Fc gamma RIIB1. Science 268:293–297.

    PubMed  CAS  Google Scholar 

  • Davidson, D., Bakinowski, M., Thomas, M. L., Horejsi, V., and Veillette, A. (2003). Phosphorylation-dependent regulation of T-cell activation by PAG/Cbp, a lipid raft-associated transmembrane adaptor. Mol Cell Biol 23:2017–2028.

    PubMed  CAS  Google Scholar 

  • Dix, A. R., Brooks, W. H., Roszman, T. L., and Morford, L. A. (1999). Immune defects observed in patients with primary malignant brain tumors. J Neuroimmunol 100:216–232.

    PubMed  CAS  Google Scholar 

  • Dolcetti, R., Viel, A., Doglioni, C., et al. (1999). High prevalence of activated intraepithelial cytotoxic T lymphocytes and increased neoplastic cell apoptosis in colorectal carcinomas with microsatellite instability. Am J Pathol 154:1805–1813.

    PubMed  CAS  Google Scholar 

  • Dukers, D. F., Oudejans, J. J., Jaspars, E. H., et al. (2000). All infiltrating T-lymphocytes in Hodgkin’s disease express immunohistochemically detectable T-cell receptor zeta-chains in situ. Histopathology 36:544–550.

    PubMed  CAS  Google Scholar 

  • Dumontet, C., Rebbaa, A., Bienvenu, J., and Portoukalian, J. (1994). Inhibition of immune cell proliferation and cytokine production by lipoprotein-bound gangliosides. Cancer Immunol Immunother 38:311–316.

    PubMed  CAS  Google Scholar 

  • Fernandez-Miguel, G., Alarcon, B., Iglesias, A., et al. (1999). Multivalent structure of an alphabetaT cell receptor. Proc Natl Acad Sci USA 96:1547–1552.

    PubMed  CAS  Google Scholar 

  • Finke, J. H., Zea, A. H., Stanley, J., et al. (1993). Loss of T-cell receptor zeta chain and p56lck in T-cells infiltrating human renal cell carcinoma. Cancer Res 53:5613–5616.

    PubMed  CAS  Google Scholar 

  • Franco, J. L., Ghosh, P., Wiltrout, R. H., et al. (1995). Partial degradation of T-cell signal transduction molecules by contaminating granulocytes during protein extraction of splenic T cells from tumor-bearing mice. Cancer Res 55:3840–3846.

    PubMed  CAS  Google Scholar 

  • Frey, A. B., and Monu, N. (2006). Effector-phase tolerance: another mechanism of how cancer escapes antitumor immune response. J Leukoc Biol 79:652–662.

    PubMed  CAS  Google Scholar 

  • Gabrilovich, D. (2004). Mechanisms and functional significance of tumour-induced dendritic-cell defects. Nat Rev Immunol 4:941–952.

    PubMed  CAS  Google Scholar 

  • Gastman, B. R., Johnson, D. E., Whiteside, T. L., and Rabinowich, H. (1999). Caspase-mediated degradation of T-cell receptor zeta-chain. Cancer Res 59:1422–1427.

    PubMed  CAS  Google Scholar 

  • Gattinoni, L., Powell, D. J., Jr, Rosenberg, S. A., and Restifo, N. P. (2006). Adoptive immuno-therapy for cancer: building on success. Nat Rev Immunol 6:383–393.

    PubMed  CAS  Google Scholar 

  • Goodwin, J. S., Bromberg, S., and Messner, R. P. (1981). Studies on the cyclic AMP response to prostaglandin in human lymphocytes. Cell Immunol 60:298–307.

    PubMed  CAS  Google Scholar 

  • Guilloux, Y., Lucas, S., Brichard, V. G., et al. (1996). A peptide recognized by human cytolytic T lymphocytes on HLA-A2 melanomas is encoded by an intron sequence of the N-acetylglucosaminyltransferase V gene. J Exp Med 183:1173–1183.

    PubMed  CAS  Google Scholar 

  • Hakomori, S. (1996). Tumor malignancy defined by aberrant glycosylation and sphingo(glyco)lipid metabolism. Cancer Res 56:5309–5318.

    PubMed  CAS  Google Scholar 

  • Hawash, I. Y., Kesavan, K. P., Magee, A. I., Geahlen, R. L., and Harrison, M. L. (2002). The Lck SH3 domain negatively regulates localization to lipid rafts through an interaction with c-Cbl. J Biol Chem 277:5683–5691.

    PubMed  CAS  Google Scholar 

  • Hayashi, S., Witte, P. L., Shultz, L. D., and Kincade, P. W. (1988). Lymphohemopoiesis in culture is prevented by interaction with adherent bone marrow cells from mutant viable motheaten mice. J Immunol 140:2139–2147.

    PubMed  CAS  Google Scholar 

  • Hernandez, J. D., and Baum, L. G. (2002). Ah, sweet mystery of death! Galectins and control of cell fate. Glycobiology 12:127R–136R.

    Google Scholar 

  • Horna, P., Cuenca, A., Cheng, F., et al. (2006). In vivo disruption of tolerogenic cross-presentation mechanisms uncovers an effective T-cell activation by B-cell lymphomas leading to antitumor immunity. Blood 107:2871–2878.

    PubMed  CAS  Google Scholar 

  • Hur, E. M., Son, M., Lee, O. H., et al. (2003). LIME, a novel transmembrane adaptor protein, associates with p56lck and mediates T cell activation. J Exp Med 198:1463–1473.

    PubMed  CAS  Google Scholar 

  • Ishikawa, T., Fujita, T., Suzuki, Y., et al. (2003). Tumor-specific immunological recognition of frameshift-mutated peptides in colon cancer with microsatellite instability. Cancer Res 63:5564–5572.

    PubMed  CAS  Google Scholar 

  • Itoh, M., Yoshida, Y., Nishida, K., Narimatsu, M., Hibi, M., and Hirano, T. (2000). Role of Gab1 in heart, placenta, and skin development and growth factor- and cytokine-induced extracellular signal-regulated kinase mitogen-activated protein kinase activation. Mol Cell Biol 20: 3695–3704.

    PubMed  CAS  Google Scholar 

  • Joung, I., Kim, T., Stolz, L. A., et al. (1995). Modification of Ser59 in the unique N-terminal region of tyrosine kinase p56lck regulates specificity of its Src homology 2 domain. Proc Natl Acad Sci USA 92:5778–5782.

    PubMed  CAS  Google Scholar 

  • Kabouridis, P. S., Magee, A. I., and Ley, S. C. (1997). S-acylation of LCK protein tyrosine kinase is essential for its signalling function in T lymphocytes. EMBO J 16:4983–4998.

    PubMed  CAS  Google Scholar 

  • Kagi, D., Ledermann, B., Burki, K., Zinkernagel, R. M., and Hengartner, H. (1996). Molecular mechanisms of lymphocyte-mediated cytotoxicity and their role in immunological protection and pathogenesis in vivo. Annu Rev Immunol 14:207–232.

    PubMed  CAS  Google Scholar 

  • Kammer, G. M. (1988). The adenylate cyclase-cAMP-protein kinase A pathway and regulation of the immune response. Immunol Today 9:222–229.

    PubMed  CAS  Google Scholar 

  • Kane, L. P., Lin, J., and Weiss, A. (2000). Signal transduction by the TCR for antigen. Curr Opin Immunol 12:242–249.

    PubMed  CAS  Google Scholar 

  • Kautz, B., Kakar, R., David, E., and Eklund, E. A. (2001). SHP1 protein-tyrosine phosphatase inhibits gp91PHOX and p67PHOX expression by inhibiting interaction of PU.1, IRF1, interferon consensus sequence-binding protein, and CREB-binding protein with homologous Cis elements in the CYBB and NCF2 genes. J Biol Chem 276:37868–37878.

    PubMed  CAS  Google Scholar 

  • Kiessling, R., Wasserman, K., Horiguchi, S., et al. (1999). Tumor-induced immune dysfunction. Cancer Immunol Immunother 48:353–362.

    PubMed  CAS  Google Scholar 

  • Kolenko, V., Wang, Q., Riedy, M. C., et al. (1997). Tumor-induced suppression of T lymphocyte proliferation coincides with inhibition of Jak3 expression and IL-2 receptor signaling: role of soluble products from human renal cell carcinomas. J Immunol 159:3057–3067.

    PubMed  CAS  Google Scholar 

  • Koneru, M., Monu, N., Schaer, D., Barletta, J., and Frey, A. B. (2006). Defective adhesion in tumor infiltrating CD8+ T cells. J Immunol 176:6103–6111.

    PubMed  CAS  Google Scholar 

  • Koneru, M., Schaer, D., Monu, N., Ayala, A., and Frey, A. B. (2005). Defective proximal TCR signaling inhibits CD8+ tumor-infiltrating lymphocyte lytic function. J Immunol 174: 1830–1840.

    PubMed  CAS  Google Scholar 

  • Kong, Y., Li, R., and Ladisch, S. (1998). Natural forms of shed tumor gangliosides. Biochim Biophys Acta 1394:43–56.

    PubMed  CAS  Google Scholar 

  • Kono, K., Salazar-Onfray, F., Petersson, M., et al. (1996). Hydrogen peroxide secreted by tumor-derived macrophages down-modulates signal-transducing zeta molecules and inhibits tumor-specific T cell-and natural killer cell-mediated cytotoxicity. Eur J Immunol 26: 1308–1313.

    PubMed  CAS  Google Scholar 

  • Kopitz, J., von Reitzenstein, C., Burchert, M., Cantz, M., and Gabius, H. J. (1998). Galectin-1 is a major receptor for ganglioside GM1, a product of the growth-controlling activity of a cell surface ganglioside sialidase, on human neuroblastoma cells in culture. J Biol Chem 273: 11205–11211.

    PubMed  CAS  Google Scholar 

  • Ladisch, S., Ulsh, L., Gillard, B., and Wong, C. (1984). Modulation of the immune response by gangliosides. Inhibition of adherent monocyte accessory function in vitro. J Clin Invest 74:2074–2081.

    PubMed  CAS  Google Scholar 

  • Ledbetter, J. A., Parsons, M., Martin, P. J., Hansen, J. A., Rabinovitch, P. S., and June, C. H. (1986). Antibody binding to CD5 (Tp67) and Tp44 T cell surface molecules: effects on cyclic nucleotides, cytoplasmic free calcium, and cAMP-mediated suppression. J Immunol 137: 3299–3305.

    PubMed  CAS  Google Scholar 

  • Lee, P. P., Yee, C., Savage, P. A., et al. (1999). Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients. Nat Med 5:677–685.

    PubMed  CAS  Google Scholar 

  • Levey, D. L., and Srivastava, P. K. (1995). T cells from late tumor-bearing mice express normal levels of p56lck, p59fyn, ZAP-70, and CD3 zeta despite suppressed cytolytic activity. J Exp Med 182:1029–1036.

    PubMed  CAS  Google Scholar 

  • Levy, F. O., Rasmussen, A. M., Tasken, K., et al. (1996). Cyclic AMP-dependent protein kinase (cAK) in human B cells: co-localization of type I cAK (RI alpha 2 C2) with the antigen receptor during anti-immunoglobulin-induced B cell activation. Eur J Immunol 26:1290–1296.

    PubMed  CAS  Google Scholar 

  • Li, X., Liu, J., Park, J. K., et al. (1994). T cells from renal cell carcinoma patients exhibit an abnormal pattern of kappa B-specific DNA-binding activity: a preliminary report. Cancer Res 54:5424–5429.

    PubMed  CAS  Google Scholar 

  • Lindahl, K. F. (1991). Do we need a pepton hypothesis? Immunogenetics 34:1–4.

    PubMed  CAS  Google Scholar 

  • Ling, W., Rayman, P., Uzzo, R., et al. (1998). Impaired activation of NFkappaB in T cells from a subset of renal cell carcinoma patients is mediated by inhibition of phosphorylation and degradation of the inhibitor, IkappaBalpha. Blood 92:1334–1341.

    PubMed  CAS  Google Scholar 

  • Liu, Y., Li, R., and Ladisch, S. (2004). Exogenous ganglioside GD1a enhances epidermal growth factor receptor binding and dimerization. J Biol Chem 279:36481–36489.

    PubMed  CAS  Google Scholar 

  • Liu, Y. C., Penninger, J., and Karin, M. (2005). Immunity by ubiquitylation: a reversible process of modification. Nat Rev Immunol 5:941–952.

    PubMed  CAS  Google Scholar 

  • Loeffler, C. M., Smyth, M. J., Longo, D. L., et al. (1992). Immunoregulation in cancer-bearing hosts. Down-regulation of gene expression and cytotoxic function in CD8+ T cells. J Immunol 149:949–956.

    PubMed  CAS  Google Scholar 

  • Lorenz, U., Ravichandran, K. S., Burakoff, S. J., and Neel, B. G. (1996). Lack of SHPTP1 results in src-family kinase hyperactivation and thymocyte hyperresponsiveness. Proc Natl Acad Sci USA 93:9624–9629.

    PubMed  CAS  Google Scholar 

  • Lupetti, R., Pisarra, P., Verrecchia, A., et al. (1998). Translation of a retained intron in tyrosinase-related protein (TRP) 2† mRNA generates a new cytotoxic T lymphocyte (CTL)-defined and shared human melanoma antigen not expressed in normal cells of the melanocytic lineage. J Exp Med 188:1005–1016.

    PubMed  CAS  Google Scholar 

  • Magee, A. I., Adler, J., and Parmryd, I. (2005). Cold-induced coalescence of T-cell plasma membrane microdomains activates signalling pathways. J Cell Sci 118:3141–3151.

    PubMed  CAS  Google Scholar 

  • Marth, J. D., Lewis, D. B., Wilson, C. B., Gearn, M. E., Krebs, E. G., and Perlmutter, R. M. (1987). Regulation of pp56lck during T-cell activation: functional implications for the src-like protein tyrosine kinases. EMBO J 6:2727–2734.

    PubMed  CAS  Google Scholar 

  • Masopust, D., Vezys, V., Marzo, A. L., and Lefrancois, L. (2001). Preferential localization of effector memory cells in nonlymphoid tissue. Science 291:2413–2417.

    PubMed  CAS  Google Scholar 

  • Meng, T. C., Fukada, T., and Tonks, N. K. (2002). Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo. Mol Cell 9:387–399.

    PubMed  CAS  Google Scholar 

  • Mescher, M. F., Curtsinger, J. M., Agarwal, P., et al. (2006). Signals required for programming effector and memory development by CD8+ T cells. Immunol Rev 211:81–92.

    PubMed  CAS  Google Scholar 

  • Michel, J. J., and Scott, J. D. (2002). AKAP mediated signal transduction. Annu Rev Pharmacol Toxicol 42:235–257.

    PubMed  CAS  Google Scholar 

  • Mizoguchi, H., O’Shea, J. J., Longo, D. L., Loeffler, C. M., McVicar, D. W., and Ochoa, A. C. (1992). Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice. Science 258:1795–1798.

    PubMed  CAS  Google Scholar 

  • Mor, A., and Philips, M. R. (2006). Compartmentalized Ras/MAPK signaling. Annu Rev Immunol 24:771–800.

    PubMed  CAS  Google Scholar 

  • Morgan, M. M., Labno, C. M., Van Seventer, G. A., Denny, M. F., Straus, D. B., and Burkhardt, J. K. (2001). Superantigen-induced T cell:B cell conjugation is mediated by LFA-1 and requires signaling through Lck, but not ZAP-70. J Immunol 167:5708–5718.

    PubMed  CAS  Google Scholar 

  • Mustelin, T., Vang, T., and Bottini, N. (2005). Protein tyrosine phosphatases and the immune response. Nat Rev Immunol 5:43–57.

    PubMed  CAS  Google Scholar 

  • Nada, S., Okada, M., MacAuley, A., Cooper, J. A., and Nakagawa, H. (1991). Cloning of a complementary DNA for a protein-tyrosine kinase that specifically phosphorylates a negative regulatory site of p60c-src. Nature 351:69–72.

    PubMed  CAS  Google Scholar 

  • Nakagomi, H., Petersson, M., Magnusson, I., et al. (1993). Decreased expression of the signal-transducing zeta chains in tumor-infiltrating T-cells and NK cells of patients with colorectal carcinoma. Cancer Res 53:5610–5612.

    PubMed  CAS  Google Scholar 

  • Neel, B. G. (1997). Role of phosphatases in lymphocyte activation. Curr Opin Immunol 9:405–420.

    PubMed  CAS  Google Scholar 

  • Oh, P., and Schnitzer, J. E. (2001). Segregation of heterotrimeric G proteins in cell surface microdomains. G(q) binds caveolin to concentrate in caveolae, whereas G(i) and G(s) target lipid rafts by default. Mol Biol Cell 12:685–698.

    PubMed  CAS  Google Scholar 

  • O’Keefe, T. L., Williams, G. T., Davies, S. L., and Neuberger, M. S. (1996). Hyperresponsive B cells in CD22-deficient mice. Science 274:798–801.

    PubMed  CAS  Google Scholar 

  • Olszowy, M. W., Leuchtmann, P. L., Veillette, A., and Shaw, A. S. (1995). Comparison of p56lck and p59fyn protein expression in thymocyte subsets, peripheral T cells, NK cells, and lymphoid cell lines. J Immunol 155:4236–4240.

    PubMed  CAS  Google Scholar 

  • Ostergaard, H. L., Shackelford, D. A., Hurley, T. R., et al. (1989). Expression of CD45 alters phosphorylation of the lck-encoded tyrosine protein kinase in murine lymphoma T-cell lines. Proc Natl Acad Sci USA 86:8959–8963.

    PubMed  CAS  Google Scholar 

  • Overwijk, W. W., Theoret, M. R., Finkelstein, S. E., et al. (2003). Tumor regression and autoimmunity after reversal of a functionally tolerant state of self-reactive CD8+ T cells. J Exp Med 198:569–580.

    PubMed  CAS  Google Scholar 

  • Pardoll, D. (2003). Does the immune system see tumors as foreign or self? Annu Rev Immunol 21:807–839.

    PubMed  CAS  Google Scholar 

  • Parmiani, G., Pilla, L., Castelli, C., and Rivoltini, L. (2003). Vaccination of patients with solid tumours. Ann Oncol 14:817–824.

    PubMed  CAS  Google Scholar 

  • Pei, D., Lorenz, U., Klingmuller, U., Neel, B. G., and Walsh, C. T. (1994). Intramolecular regulation of protein tyrosine phosphatase SH-PTP1: a new function for Src homology 2 domains. Biochemistry 33:15483–15493.

    PubMed  CAS  Google Scholar 

  • Perry, S. J., Baillie, G. S., Kohout, T. A., et al. (2002). Targeting of cyclic AMP degradation to beta 2-adrenergic receptors by beta-arrestins. Science 298:834–836.

    PubMed  CAS  Google Scholar 

  • Perry, S. J., and Lefkowitz, R. J. (2002). Arresting developments in heptahelical receptor signaling and regulation. Trends Cell Biol 12:130–138.

    PubMed  CAS  Google Scholar 

  • Plas, D. R., Johnson, R., Pingel, J. T., et al. (1996). Direct regulation of ZAP-70 by SHP-1 in T cell antigen receptor signaling. Science 272:1173–1176.

    PubMed  CAS  Google Scholar 

  • Pope, C., Kim, S. K., Marzo, A., et al. (2001). Organ-specific regulation of the CD8 T cell response to Listeria monocytogenes infection. J Immunol 166:3402–3409.

    CAS  Google Scholar 

  • Rabinovich, G., Gabrilovich, D., and Sotomayer, E. (2007). Immunosuppressive strategies that are mediated by tumor cells. Annu Rev Immunol 25:267–296.

    PubMed  CAS  Google Scholar 

  • Radoja, S., Frey, A. B., and Vukmanovic, S. (2006). T-cell receptor signaling events triggering granule exocytosis. Crit Rev Immunol 26:265–290.

    PubMed  CAS  Google Scholar 

  • Radoja, S., Rao, T. D., Hillman, D., and Frey, A. B. (2000). Mice bearing late-stage tumors have normal functional systemic T cell responses in vitro and in vivo. J Immunol 164: 2619–2628.

    PubMed  CAS  Google Scholar 

  • Radoja, S., Saio, M., Schaer, D., Koneru, M., Vukmanovic, S., and Frey, A. B. (2001). CD8(+) tumor-infiltrating T cells are deficient in perforin-mediated cytolytic activity due to defective microtubule-organizing center mobilization and lytic granule exocytosis. J Immunol 167: 5042–5051.

    PubMed  CAS  Google Scholar 

  • Ravetch, J. V., and Kinet, J. P. (1991). Fc receptors. Annu Rev Immunol 9:457–492.

    PubMed  CAS  Google Scholar 

  • Reichert, T. E., Strauss, L., Wagner, E. M., Gooding, W., and Whiteside, T. L. (2002). Signaling abnormalities, apoptosis, and reduced proliferation of circulating and tumor-infiltrating lymphocytes in patients with oral carcinoma. Clin Cancer Res 8:3137–3145.

    PubMed  Google Scholar 

  • Resh, M. D. (1994). Myristylation and palmitylation of Src family members: the fats of the matter. Cell 76:411–413.

    PubMed  CAS  Google Scholar 

  • Riedl, K., Krysan, K., Pold, M., et al. (2004). Multifaceted roles of cyclooxygenase-2 in lung cancer. Drug Resist Updat 7:169–184.

    PubMed  CAS  Google Scholar 

  • Ritter, G., and Livingston, P. O. (1991). Ganglioside antigens expressed by human cancer cells. Semin Cancer Biol 2:401–409.

    PubMed  CAS  Google Scholar 

  • Rodriguez, P. C., Hernandez, C. P., Quiceno, D., et al. (2005). Arginase I in myeloid suppressor cells is induced by COX-2 in lung carcinoma. J Exp Med 202:931–939.

    PubMed  CAS  Google Scholar 

  • Rosenberg, S. A., Yang, J. C., and Restifo, N. P. (2004). Cancer immunotherapy: moving beyond current vaccines. Nat Med 10:909–915.

    PubMed  CAS  Google Scholar 

  • Rudd, C. E. (1999). Adaptors and molecular scaffolds in immune cell signaling. Cell 96:5–8.

    PubMed  CAS  Google Scholar 

  • Sachs, M., Brohmann, H., Zechner, D., et al. (2000). Essential role of Gab1 for signaling by the c-Met receptor in vivo. J Cell Biol 150:1375–1384.

    PubMed  CAS  Google Scholar 

  • Samelson, L. E. (2002). Signal transduction mediated by the T cell antigen receptor: the role of adapter proteins. Annu Rev Immunol 20:371–394.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Schraven, B., Marie-Cardine, A., Hubener, C., Bruyns, E., and Ding, I. (1999). Integration of receptor-mediated signals in T cells by transmembrane adaptor proteins. Immunol Today 20:431–434.

    PubMed  CAS  Google Scholar 

  • Shu, S., Cochran, A. J., Huang, R. R., Morton, D. L., and Maecker, H. T. (2006). Immune responses in the draining lymph nodes against cancer: implications for immunotherapy. Cancer Metastasis Rev 25:233–242.

    PubMed  Google Scholar 

  • Shultz, L. D., Schweitzer, P. A., Rajan, T. V., et al. (1993). Mutations at the murine motheaten locus are within the hematopoietic cell protein-tyrosine phosphatase (Hcph) gene. Cell 73: 1445–1454.

    PubMed  CAS  Google Scholar 

  • Siminovitch, K. A., and Neel, B. G. (1998). Regulation of B cell signal transduction by SH2-containing protein-tyrosine phosphatases. Semin Immunol 10:329–347.

    PubMed  CAS  Google Scholar 

  • Sloan-Lancaster, J., and Allen, P. M. (1996). Altered peptide ligand-induced partial T cell activation: molecular mechanisms and role in T cell biology. Annu Rev Immunol 14:1–27.

    PubMed  CAS  Google Scholar 

  • Sloan-Lancaster, J., Steinberg, T. H., and Allen, P. M. (1996). Selective activation of the calcium signaling pathway by altered peptide ligands. J Exp Med 184:1525–1530.

    PubMed  CAS  Google Scholar 

  • Staveley-O’Carroll, K., Sotomayor, E., Montgomery, J., et al. (1998). Induction of antigen-specific T cell anergy: an early event in the course of tumor progression. Proc Natl Acad Sci USA 95:1178–1183.

    PubMed  CAS  Google Scholar 

  • Stefanova, I., Hemmer, B., Vergelli, M., Martin, R., Biddison, W. E., and Germain, R. N. (2003). TCR ligand discrimination is enforced by competing ERK positive and SHP-1 negative feedback pathways. Nat Immunol 4:248–254.

    PubMed  CAS  Google Scholar 

  • Stulnig, T. M., Berger, M., Sigmund, T., Raederstorff, D., Stockinger, H., and Waldhausl, W. (1998). Polyunsaturated fatty acids inhibit T cell signal transduction by modification of detergent-insoluble membrane domains. J Cell Biol 143:637–644.

    PubMed  CAS  Google Scholar 

  • Stutman, O. (1975). Immunodepression and malignancy. Adv Cancer Res 22:261–422.

    PubMed  CAS  Google Scholar 

  • Takahashi-Tezuka, M., Yoshida, Y., Fukada, T., et al. (1998). Gab1 acts as an adapter molecule linking the cytokine receptor gp130 to ERK mitogen-activated protein kinase. Mol Cell Biol 18:4109–4117.

    PubMed  CAS  Google Scholar 

  • Tasken, K., and Aandahl, E. M. (2004). Localized effects of cAMP mediated by distinct routes of protein kinase A. Physiol Rev 84:137–167.

    PubMed  CAS  Google Scholar 

  • Tasken, K., and Stokka, A. J. (2006). The molecular machinery for cAMP-dependent immunomodulation in T-cells. Biochem Soc Trans 34:476–479.

    PubMed  CAS  Google Scholar 

  • Tedoldi, S., Paterson, J. C., Hansmann, M. L., et al. (2006). Transmembrane adaptor molecules: a new category of lymphoid-cell markers. Blood 107:213–221.

    PubMed  CAS  Google Scholar 

  • Thornton, M. V., Kudo, D., Rayman, P., et al. (2004). Degradation of NF-kappa B in T cells by gangliosides expressed on renal cell carcinomas. J Immunol 172:3480–3490.

    PubMed  CAS  Google Scholar 

  • Torgersen, K. M., Vaage, J. T., Levy, F. O., Hansson, V., Rolstad, B., and Tasken, K. (1997). Selective activation of cAMP-dependent protein kinase type I inhibits rat natural killer cell cytotoxicity. J Biol Chem 272:5495–5500.

    PubMed  CAS  Google Scholar 

  • Torgersen, K. M., Vang, T., Abrahamsen, H., et al. (2001). Release from tonic inhibition of T cell activation through transient displacement of C-terminal Src kinase (Csk) from lipid rafts. J Biol Chem 276:29313–29318.

    PubMed  CAS  Google Scholar 

  • Torgersen, K. M., Vang, T., Abrahamsen, H., Yaqub, S., and Tasken, K. (2002). Molecular mechanisms for protein kinase A-mediated modulation of immune function. Cell Signal 14:1–9.

    PubMed  CAS  Google Scholar 

  • Tran, D. D., Edgar, C. E., Heckman, K. L., et al. (2005). CAML is a p56Lck-interacting protein that is required for thymocyte development. Immunity 23:139–152.

    PubMed  CAS  Google Scholar 

  • Uzzo, R. G., Clark, P. E., Rayman, P., et al. (1999a). Alterations in NFkappaB activation in T lymphocytes of patients with renal cell carcinoma. J Natl Cancer Inst 91:718–721.

    CAS  Google Scholar 

  • Uzzo, R. G., Rayman, P., Kolenko, V., et al. (1999b). Mechanisms of apoptosis in T cells from patients with renal cell carcinoma. Clin Cancer Res 5:1219–1229.

    CAS  Google Scholar 

  • Valitutti, S., Muller, S., Salio, M., and Lanzavecchia, A. (1997). Degradation of T cell receptor (TCR)-CD3-zeta complexes after antigenic stimulation. J Exp Med 185:1859–1864.

    PubMed  CAS  Google Scholar 

  • Vang, T., Torgersen, K. M., Sundvold, V., et al. (2001). Activation of the COOH-terminal Src kinase (Csk) by cAMP-dependent protein kinase inhibits signaling through the T cell receptor. J Exp Med 193:497–507.

    PubMed  CAS  Google Scholar 

  • Varki, A., and Angata, T. (2006). Siglecs—the major subfamily of I-type lectins. Glycobiology 16:1R–27R.

    Google Scholar 

  • Veillette, A., Horak, I. D., Horak, E. M., Bookman, M. A., and Bolen, J. B. (1988). Alterations of the lymphocyte-specific protein tyrosine kinase (p56lck) during T-cell activation. Mol Cell Biol 8:4353–4361.

    PubMed  CAS  Google Scholar 

  • Vivier, E., and Anfossi, N. (2004). Inhibitory NK-cell receptors on T cells: witness of the past, actors of the future. Nat Rev Immunol 4:190–198.

    PubMed  CAS  Google Scholar 

  • Vivier, E., and Daeron, M. (1997). Immunoreceptor tyrosine-based inhibition motifs. Immunol Today 18:286–291.

    PubMed  CAS  Google Scholar 

  • Wang, Q., Stanley, J., Kudoh, S., et al. (1995). T cells infiltrating non-Hodgkin’s B cell lymphomas show altered tyrosine phosphorylation pattern even though T cell receptor/CD3-associated kinases are present. J Immunol 155:1382–1392.

    PubMed  CAS  Google Scholar 

  • Watts, J. D., Sanghera, J. S., Pelech, S. L., and Aebersold, R. (1993). Phosphorylation of serine 59 of p56lck in activated T cells. J Biol Chem 268:23275–23282.

    PubMed  CAS  Google Scholar 

  • Weiss, A., and Littman, D. R. (1994). Signal transduction by lymphocyte antigen receptors. Cell 76:263–274.

    PubMed  CAS  Google Scholar 

  • Whiteside, T. L. (1998). Immune cells in the tumor microenvironment. Mechanisms responsible for functional and signaling defects. Adv Exp Med Biol 451:167–171.

    PubMed  CAS  Google Scholar 

  • Whiteside, T. L. (1999). Signaling defects in T lymphocytes of patients with malignancy. Cancer Immunol Immunother 48:346–352.

    PubMed  CAS  Google Scholar 

  • Whiteside, T. L. (2004). Down-regulation of zeta-chain expression in T cells: a biomarker of prognosis in cancer? Cancer Immunol Immunother 53:865–878.

    PubMed  CAS  Google Scholar 

  • Whiteside, T. L., and Parmiani, G. (1994). Tumor-infiltrating lymphocytes: their phenotype, functions and clinical use. Cancer Immunol Immunother 39:15–21.

    PubMed  CAS  Google Scholar 

  • Wick, M., Dubey, P., Koeppen, H., et al. (1997). Antigenic cancer cells grow progressively in immune hosts without evidence for T cell exhaustion or systemic anergy. J Exp Med 186: 229–238.

    PubMed  CAS  Google Scholar 

  • Willimsky, G., and Blankenstein, T. (2005). Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance. Nature 437:141–146.

    PubMed  CAS  Google Scholar 

  • Winkler, D. G., Park, I., Kim, T., et al. (1993). Phosphorylation of Ser-42 and Ser-59 in the N-terminal region of the tyrosine kinase p56lck. Proc Natl Acad Sci USA 90:5176–5180.

    PubMed  CAS  Google Scholar 

  • Wolfl, M., Batten, W. Y., Posovszky, C., Bernhard, H., and Berthold, F. (2002). Gangliosides inhibit the development from monocytes to dendritic cells. Clin Exp Immunol 130:441–448.

    PubMed  CAS  Google Scholar 

  • Zamoyska, R. (1998). CD4 and CD8: modulators of T-cell receptor recognition of antigen and of immune responses? Curr Opin Immunol 10:82–87.

    PubMed  CAS  Google Scholar 

  • Zhang, S. Q., Yang, W., Kontaridis, M. I., et al. (2004). Shp2 regulates SRC family kinase activity and Ras/Erk activation by controlling Csk recruitment. Mol Cell 13:341–355.

    PubMed  Google Scholar 

  • Zhang, Z., Shen, K., Lu, W., and Cole, P. A. (2003). The role of C-terminal tyrosine phosphorylation in the regulation of SHP-1 explored via expressed protein ligation. J Biol Chem 278: 4668–4674.

    PubMed  CAS  Google Scholar 

  • Zhou, G., Drake, C. G., and Levitsky, H. I. (2006). Amplification of tumor-specific regulatory T cells following therapeutic cancer vaccines. Blood 107:628–636.

    PubMed  CAS  Google Scholar 

  • Zou, W. (2005). Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer 5:263–274.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cell Biology-MSB623, New York University School ofMedicine, 550 First Avenue, New York, NY 10016, USA

    Alan B. Frey

Authors
  1. Alan B. Frey
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL 33612, USA

    Dmitry I. Gabrilovich

  2. Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick, MD 21071, USA

    Arthur A. Hurwitz

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Frey, A.B. (2008). Cancer-Induced Signaling Defects in Antitumor T Cells. In: Gabrilovich, D.I., Hurwitz, A.A. (eds) Tumor-Induced Immune Suppression. Springer, New York, NY. https://doi.org/10.1007/978-0-387-69118-3_5

Download citation

Publish with us

Policies and ethics

Search

Navigation