• 1
    Muranski, P., Boni, A., Antony, P. A., Cassard, L., Irvine, K. R., Kaiser, A., Paulos, C. M. et al., Tumor-specific Th17-polarized cells eradicate large established melanoma. Blood 2008. 112: 362373.
  • 2
    Xie, Y., Akpinarli, A., Maris, C., Hipkiss, E. L., Lane, M., Kwon, E. K., Muranski, P. et al., Naive tumor-specific CD4(+) T cells differentiated in vivo eradicate established melanoma. J. Exp. Med. 2010. 207: 651667.
  • 3
    Fujiwara, H., Fukuzawa, M., Yoshioka, T., Nakajima, H. and Hamaoka, T., The role of tumor-specific Lyt-1+2- T cells in eradicating tumor cells in vivo. I. Lyt-1+2- T cells do not necessarily require recruitment of host's cytotoxic T cell precursors for implementation of in vivo immunity. .J Immunol. 1984. 133: 16711676.
  • 4
    Greenberg, P. D., Kern, D. E. and Cheever, M. A., Therapy of disseminated murine leukemia with cyclophosphamide and immune Lyt-1+,2- T cells. Tumor eradication does not require participation of cytotoxic T cells. J. Exp. Med. 1985. 161: 11221134.
  • 5
    Quezada, S. A., Simpson, T. R., Peggs, K. S., Merghoub, T., Vider, J., Fan, X., Blasberg, R. et al., Tumor-reactive CD4+ T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts. J. Exp. Med. 2010. 207: 637650.
  • 6
    Mumberg, D., Monach, P. A., Wanderling, S., Philip, M., Toledano, A. Y., Schreiber, R. D. and Schreiber, H., CD4(+) T cells eliminate MHC class II-negative cancer cells in vivo by indirect effects of IFN-gamma. Proc. Natl. Acad. Sci. U S A 1999. 96: 86338638.
  • 7
    Bogen, B., Munthe, L., Sollien, A., Hofgaard, P., Omholt, H., Dagnaes, F., Dembic, Z. et al., Naive CD4+ T cells confer idiotype-specific tumor resistance in the absence of antibodies. Eur. J. Immunol. 1995. 25: 30793086.
  • 8
    Perez-Diez, A., Joncker, N. T., Choi, K., Chan, W. F. N., Anderson, C. C., Lantz, O. and Matzinger, P., CD4 cells can be more efficient at tumor rejection than CD8 cells. Blood 2007. 109: 53465354.
  • 9
    Gao, F. G., Khammanivong, V., Liu, W. J., Leggatt, G. R., Frazer, I. H. and Fernando, G. J. P., Antigen-specific CD4(+) T-cell help is required to activate a memory CD8(+) T cell to a fully functional tumor killer cell. Cancer Res. 2002. 62: 64386441.
  • 10
    Antony, P. A., Piccirillo, C. A., Akpinarli, A., Finkelstein, S. E., Speiss, P. J., Surman, D. R., Palmer, D. C. et al., CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cells. J. Immunol. 2005. 174: 25912601.
  • 11
    Janssen, E. M., Lemmens, E. E., Wolfe, T., Christen, U., von Herrath, M. G. and Schoenberger, S. P., CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes. Nature 2003. 421: 852856.
  • 12
    Tite, J. P. and Janeway, C. A., Jr., Cloned helper T cells can kill B lymphoma cells in the presence of specific antigen: Ia restriction and cognate vs. noncognate interactions in cytolysis. Eur. J. Immunol. 1984. 14: 878886.
  • 13
    Lauritzsen, G. F., Weiss, S., Dembic, Z. and Bogen, B., Naive idiotype-specific CD4+ T cells and immunosurveillance of B-cell tumors. Proc. Natl. Acad. Sci. U S A 1994. 91: 57005704.
  • 14
    Lundin, K. U., Screpanti, V., Omholt, H., Hofgaard, P. O., Yagita, H., Grandien, A. and Bogen, B., CD4+ T cells kill Id+ B-lymphoma cells: FasLigand-Fas interaction is dominant in vitro but is redundant in vivo. Cancer Immunol. Immunother. 2004. 53: 11351145.
  • 15
    Qin, Z. H. and Blankenstein, T., CD4(+) T cell-mediated tumor rejection involves inhibition of angiogenesis that is dependent on IFN gamma receptor expression by nonhematopoietic cells. Immunity 2000. 12: 677686.
  • 16
    Corthay, A., Skovseth, D. K., Lundin, K. U., Røsjø, E., Omholt, H., Hofgaard, P. O., Haraldsen, G. et al., Primary antitumor immune response mediated by CD4+ T cells. Immunity 2005. 22: 371383.
  • 17
    Corthay, A., Lundin, K. U., Lorvik, K. B., Hofgaard, P. O. and Bogen, B., Secretion of yumor-specific antigen by myeloma cells is required for cancer immunosurveillance by CD4+ T cells. Cancer Res. 2009. 69: 59015907.
  • 18
    Haabeth, O. A., Lorvik, K. B., Hammarstrom, C., Donaldson, I. M., Haraldsen, G., Bogen, B. and Corthay, A., Inflammation driven by tumour-specific Th1 cells protects against B-cell cancer. Nat. Commun. 2011. 2: 240.
  • 19
    Kerkar, S. P. and Restifo, N. P., Cellular constituents of immune escape within the tumor microenvironment. Cancer Res. 2012. 72: 31253130.
  • 20
    Garrido, F. and Ruiz-Cabello, F., MHC expression on human tumors–its relevance for local tumor growth and metastasis. Semin. Cancer Biol. 1991. 2: 310.
  • 21
    Cabrera, T., Ruiz-Cabello, F. and Garrido, F., Biological implications of HLA-DR expression in tumours. Scand. J. Immunol. 1995. 41: 398406.
  • 22
    Bogen, B., Malissen, B. and Haas, W., Idiotope-specific T cell clones that recognize syngeneic immunoglobulin fragments in the context of class II molecules. Eur. J. Immunol. 1986. 16: 13731378.
  • 23
    Bogen, B., Gleditsch, L., Weiss, S. and Dembic, Z., Weak positive selection of transgenic T cell receptor-bearing thymocytes: importance of major histocompatibility complex class II, T cell receptor and CD4 surface molecule densities. Eur. J. Immunol. 1992. 22: 703709.
  • 24
    Dembic, Z., Schenck, K. and Bogen, B., Dendritic cells purified from myeloma are primed with tumor-specific antigen (idiotype) and activate CD4+ T cells. Proc. Natl. Acad. Sci. U S A 2000. 97: 26972702.
  • 25
    Lauritzsen, G. F., Weiss, S. and Bogen, B., Anti-tumour activity of idiotype-specific, MHC-restricted Th1 and Th2 clones in vitro and in vivo. Scand. J. Immunol. 1993. 37: 7785.
  • 26
    Dembic, Z., Rottingen, J. A., Dellacasagrande, J., Schenck, K. and Bogen, B., Phagocytic dendritic cells from myelomas activate tumor-specific T cells at a single cell level. Blood 2001. 97: 28082814.
  • 27
    Lauritzsen, G. F. and Bogen, B., The role of idiotype-specific, CD4+ T cells in tumor resistance against major histocompatibility complex Class II molecule negative plasmacytoma cells. Cell Immunol. 1993. 148: 177188.
  • 28
    Buhtoiarov, I. N., Lum, H., Berke, G., Paulnock, D. M., Sondel, P. M. and Rakhmilevich, A. L., CD40 ligation activates murine macrophages via an IFN-gamma-dependent mechanism resulting in tumor cell destruction in vitro. J. Immunol. 2005. 174: 60136022.
  • 29
    Egeblad, M., Ewald, A. J., Askautrud, H. A., Truitt, M. L., Welm, B. E., Bainbridge, E., Peeters, G. et al., Visualizing stromal cell dynamics in different tumor microenvironments by spinning disk confocal microscopy. Dis. Model Mech. 2008. 1: 155167.
  • 30
    Huse, M., Lillemeier, B. F., Kuhns, M. S., Chen, D. S. and Davis, M. M., T cells use two directionally distinct pathways for cytokine secretion. Nat. Immunol. 2006. 7: 247255.
  • 31
    Kimachi, K., Croft, M. and Grey, H. M., The minimal number of antigen-major histocompatibility complex class II complexes required for activation of naive and primed T cells. Eur. J. Immunol. 1997. 27: 33103317.
  • 32
    Schietinger, A., Philip, M., Liu, R. B., Schreiber, K. and Schreiber, H., Bystander killing of cancer requires the cooperation of CD4+ and CD8+ T cells during the effector phase. J. Exp. Med. 2010. 207: 24692477.
  • 33
    Mantovani, A., Sozzani, S., Locati, M., Allavena, P. and Sica, A., Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 2002. 23: 549555.
  • 34
    Biswas, S. K., Gangi, L., Paul, S., Schioppa, T., Saccani, A., Sironi, M., Bottazzi, B. et al., A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation). Blood 2006. 107: 21122122.
  • 35
    Mantovani, A., Allavena, P., Sica, A. and Balkwill, F., Cancer-related inflammation. Nature 2008. 454: 436444.
  • 36
    Pollard, J. W., Tumour-educated macrophages promote tumour progression and metastasis. Nat. Rev. Cancer 2004. 4: 7178.
  • 37
    Solinas, G., Germano, G., Mantovani, A. and Allavena, P., Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J. Leukoc. Biol. 2009. 86: 10651073.
  • 38
    Duluc, D., Corvaisier, M., Blanchard, S., Catala, L., Descamps, P., Gamelin, E., Ponsoda, S. et al., Interferon-gamma reverses the immunosuppressive and protumoral properties and prevents the generation of human tumor-associated macrophages. Int. J. Cancer 2009. 125: 367373.
  • 39
    Heusinkveld, M., de Vos van Steenwijk, P. J., Goedemans, R., Ramwadhdoebe, T. H., Gorter, A., Welters, M. J., van Hall, T. et al., M2 macrophages induced by prostaglandin E2 and IL-6 from cervical carcinoma are switched to activated M1 macrophages by CD4+ Th1 cells. J. Immunol. 2011. 187: 11571165.
  • 40
    Allavena, P. and Mantovani, A., Immunology in the clinic review series; focus on cancer: tumour-associated macrophages: undisputed stars of the inflammatory tumour microenvironment. Clin. Exp. Immunol. 2012. 167: 195205.
  • 41
    Beatty, G. L., Chiorean, E. G., Fishman, M. P., Saboury, B., Teitelbaum, U. R., Sun, W., Huhn, R. D. et al., CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science 2011. 331: 16121616.
  • 42
    Winberry, L., Marks, A. and Baumal, R., Immunoglobulin production and secretion by variant clones of the MOPC 315 mouse myeloma cell line. J. Immunol. 1980. 124: 11741182.