• 1
    Schuler, G., Schuler-Thurner, B. and Steinman, R. M., The use of dendritic cells in cancer immunotherapy. Curr. Opin. Immunol. 2003. 15: 138147.
  • 2
    Dudley, M. E. and Rosenberg, S. A., Adoptive-cell-transfer therapy for the treatment of patients with cancer. Nat. Rev. 2003. 3: 666675.
  • 3
    Khong, H. T. and Restifo, N. P., Natural selection of tumor variants in the generation of “tumor escape” phenotypes. Nat. Immunol. 2002. 3: 9991005.
  • 4
    Marincola, F. M., Jaffee, E. M., Hicklin, D. J. and Ferrone, S., Escape of human solid tumors from T-cell recognition: molecular mechanisms and functional significance. Adv. Immunol. 2000. 74: 181273.
  • 5
    Bronte, V., Serafini, P., Apolloni, E. and Zanovello, P., Tumor-induced immune dysfunction caused by myeloid suppressor cells. J. Immunother. 2001. 24: 431446.
  • 6
    Chen, M. L., Wang, F. H., Lee, P. K. and Lin, C. M., Interleukin-10-induced T cell unresponsiveness can be reversed by dendritic cell stimulation. Immunol. Lett. 2001. 75: 9196.
  • 7
    Matthews, E., Yang, T., Janulis, L., Goodwin, S., Kundu, S. D., Karpus, W. J. and Lee, C., Down regulation of TGF-b1 production restores immunogenicity in prostate cancer cells. Brit. J. Cancer 2000. 83: 519525.
  • 8
    Sakaguchi, S., Sakaguchi, N., Shimizu, J., Yamazaki, S., Sakihama, T., Itoh, M., Kuniyasu, Y. et al., Immunologic tolerance maintained by CD25 CD4 regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol. Rev. 2001. 182: 1832.
  • 9
    Fehervari, Z. and Sakaguchi, S., CD4+ Treg and immune control. J. Clin. Invest. 2004. 114: 12091217.
  • 10
    Schoenberger, S. P., Toes, R. E., van der Voort, E., Offringa, R. and Melief, C. J., T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature 1998. 393: 480483.
  • 11
    Bennett, S. R., Carbone, F. R., Karamalis, F., Flavell, R. A., Miller, J. F. and Heath, W. R., Help for cytotoxic-T-cell responses is mediated by CD40 signalling. Nature 1998. 393: 478480.
  • 12
    Ridge, J. P., Di Rosa, F. and Matzinger, P., A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell. Nature 1998. 393: 474478.
  • 13
    Wang, R. F., The role of MHC class II-restricted tumor antigens and CD4+ T cells in antitumor immunity. Trends Immunol. 2001. 22: 269276.
  • 14
    Gao, F. G., Khammanivong, V., Liu, W. J., Leggatt, G. R., Frazer, I. H. and Fernando, J. C., 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.
  • 15
    Peggs, K. S., Quezada, S. A., Korman, A. J. and Allison, J. P., Principle and use of anti-CTLA4 antibody in human cancer immunotherapy. Curr. Opin. Immunol. 2006. 18: 206213.
  • 16
    Dighe, A. S., Richards, E., Old, L. J. and Schreiber, R. D., Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFN gamma receptors. Immunity 1994. 1: 447456.
  • 17
    Qin, Z. and Blankenstein, T., CD4+ T cell-mediated tumor rejection involves inhibition of angiogenesis that is dependent on IFNγ receptor on nonhematopoietic cells. Immunity 2000. 12: 677686.
  • 18
    Hung, K., Hayashi, R., Lafond-Walker, A., Lowenstein, C., Pardoll, D. M. and Levitsky, H., The central role of CD4+ T cells in the antitumor immune response. J. Exp. Med. 1998. 188: 23572368.
  • 19
    Schuler, T., Qin, Z., Ibe, S., Noben-Trauth, N. and Blankenstein, T., T helper cell type 1-associated and cytotoxic T lymphocyte-mediated tumor immunity is impaired in interleukin 4-deficient mice. J. Exp. Med. 1999. 189: 803810.
  • 20
    Lopez, M. V., Adris, S. K., Bravo, A. I., Chernajovsky, Y. and Podhajcer, O. L., IL-12 and IL-10 expression synergize to induce the immune-mediated eradication of established colon and mammary tumors and lung metastasis . J. Immunol. 2005. 175: 58855894.
  • 21
    Old, L. J., Tumor necrosis factor (TNF). Science 1985. 230: 630632.
  • 22
    Jones, E. Y., Stuart, D. I. and Walker, N. P. C., Structure of tumor necrosis factor. Nature 1989. 338: 225228.
  • 23
    Watanabe, N., Niitsu, Y., Umeno, H., Kuriyama, H., Neda, H., Yamauchi, N., Maeda, M. and Urushizaki, I., Toxic effect of tumor necrosis factor on tumor vasculature in mice. Cancer Res. 1988. 48: 21792183.
  • 24
    Fajardo, L. F., Kwan, H. H., Kowalski, J., Prionas, S. D. and Allison, A. C., Dual role of tumor necrosis factor-alpha in angiogenesis. Am. J. Pathol. 1992. 140: 539544.
  • 25
    Kirchhofer, D., Sakariassen, K. S., Clozel, M., Tschopp, T. B., Hadvary, P., Nemerson, Y. and Baumgartner, H. R., Relationship between tissue factor expression and deposition of fibrin, platelets, and leukocytes on cultured endothelial cells under venous blood flow conditions. Blood 1993. 81: 20502058.
  • 26
    Folli, S., Pelegrin, A., Chalandon, Y., Yao, X., Buchegger, F., Lienard, D., Lejeune, F. and Mach, J. P., Tumor-necrosis factor can enhance radio-antibody uptake in human colon carcinoma xenografts by increasing vascular permeability. Int. J. Cancer 1993. 53: 829836.
  • 27
    Kristensen, C. A., Nozue, M., Boucher, Y. and Jain, R. K., Reduction of interstitial fluid pressure after TNFalpha treatment of three human melanoma xenografts. Br. J. Cancer 1996. 74: 533536.
  • 28
    Lienard, D., Ewalenko, P., Delmotte, J. J., Renard, N. and Lejeune, F. J., High-dose recombinant tumor necrosis factor alpha in combination with interferon gamma and melphalan in isolation perfusion of the limbs for melanoma and sarcoma. J. Clin. Oncol. 1992. 10: 5260.
  • 29
    Eggermont, A. M., Schraffordt Koops, H., Lienard, D., Kroon, B. B., van Geel, A. N., Hoekstra, H. J. and Lejeune, F. J., Isolated limb perfusion with high dose tumor necrosis factor-alpha in combination with interferon-gamma an Melphalan for nonresectable extremity soft tissue sarcomas: a multicenter trial. J. Clin. Oncol. 1996. 14: 479489.
  • 30
    Castellani, P., Viale, G., Dorcaratto, A., Nicolò, G., Kaczmarek, J., Querze, G. and Zardi, L., The fibronectin isoform containing the ED-B oncofetal domain: a marker of angiogenesis. Int. J. Cancer 1994. 59: 612618.
  • 31
    Castellani, P., Borsi, L., Carnemolla, B., Biro, A., Dorcaratto, A., Viale, G. L., Neri, D. and Zardi, L., Differentiation between high and low grade astrocitoma using a human recombinant antibody to extra domain-B of fibronectin. Am. J. Pathol. 2002. 161: 16951700.
  • 32
    Tarli, L., Balza, E., Viti, F., Borsi, L., Castellani, P., Berndorff, D., Dinkelborg, L. et al., A high affinity human antibody that targets tumoral blood vessels. Blood 1999. 94: 192198.
  • 33
    Carnemolla, B., Neri, D., Castellani, P., Leprini, A., Neri, G., Pini, A., Winter, G. and Zardi, L., Phage antibodies with pan-species recognition of the oncofoetal angiogenesis marker fibronectin ED-B domain. Int. J. Cancer 1996. 68: 397405.
  • 34
    Neri, D., Carnemolla, B., Nissim, A., Leprini, A., Querce, G., Balza, E., Pini, A. et al., Targeting by affinity-matured recombinant antibody fragments of an angiogenesis associated fibronectin isoform. Nat. Biotechnol. 1997. 15: 12711275.
  • 35
    Santimaria, M., Moscatelli, G., Viale, G. L., Giovannoni, L., Neri, G., Viti, F., Leporini, A. et al., Immunoscintigraphic detection of the ED-B domain of fibronectin, a marker of angiogenesis, in patients with cancer. Clin. Cancer Res. 2003. 9: 571579.
  • 36
    Carnemolla, B., Borsi, L., Balza, E., Castellani, P., Meazza, R., Berndt, A., Ferrini, S. et al., Enhancement of the antitumor properties of interleukin-2 by its targeted delivery to the tumor blood vessel extracellular matrix. Blood 2002. 99: 16591665.
  • 37
    Halin, C., Rondini, S., Nilsson, F., Berndt, A., Kosmehl, H., Zardi, L. and Neri, D., Enhancement of the anti-tumor activity of interleukin-12 by targeted delivery to neo-vasculature. Nat. Biotechnol. 2002. 20: 264269.
  • 38
    Borsi, L., Balza, E., Carnemolla, B., Sassi, F., Castellani, P., Berndt, A., Kosmehl, H. et al., Selective targeted delivery of TNFα to tumor blood vessels. Blood 2003. 102: 43844392.
  • 39
    Balza, E., Mortara, L., Sassi, F., Monteghirfo, S., Carnemolla, B., Castellani, P., Neri, D. et al., Targeted delivery of tumor necrosis factor-α to tumor vessels induces a therapeutic T cell-mediated immune response that protects the host against syngeneic tumors of different histologic origin. Clin. Cancer Res. 2006. 12: 25752582.
  • 40
    Sakaguchi, S., Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of the immune response. Annu. Rev. Immunol. 2004. 22: 531562.
  • 41
    Mortara, L., Castellani, P., Meazza, R., Tosi, G., De Lerma Barbaro, A., Procopio, F. A., Comes, A. et al., CIITA-induced MHC class II expression in mammary adenocarcinoma leads to a Th1 polarization of the tumor microenvironment, tumor rejection, and specific antitumor memory. Clin. Cancer Res. 2006. 12: 34353443.
  • 42
    Giovarelli, M., Musini, P., Modesti, A., Dellabona, P., Castrati, G., Allione, A., Consalvo, M. et al., Local release of IL-10 by transfected mouse mammary adenocarcinoma cells does not suppress but enhances antitumor reaction and elicits a strong cytotoxic lymphocyte and antibody-dependent immune memory. J. Immunol. 1995. 155: 31123123.
  • 43
    Shimizu, J., Yamazaki, S. and Sakaguchi, S., Induction of tumor immunity by removing CD25+CD4+ T cells: a common basis between tumor immunity and autoimmunity. J. Immunol. 1999. 163: 52115218.
  • 44
    Golgher, D., Jones, E., Powrie, F., Elliott, T. and Gallimore, A., Depletion of CD25+ regulatory cells uncovers immune responses to shared murine tumor rejection antigens. Eur. J. Immunol. 2002. 32: 32673275.
  • 45
    Ehrenstein, M. R., Evans, J. G., Singh, A., Moore, S., Warnes, G., Isenberg, D. A. and Mauri C., Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFα therapy. J. Exp. Med. 2004. 200: 277285.
  • 46
    Lutsiak, M. E., Semnani, R. T., De Pascalis, R., Kashmiri, S. V., Schlom, J. and Sabzevari, H., Inhibition of CD4(+)25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. Blood 2005. 105: 28622868.
  • 47
    Dalton, D. K., Pitts-Meek, S., Keshav, S., Figari, I. S., Bradley, A. and Stewart, T. A., Multiple defects of immune cell function in mice with disrupted interferon-γ genes. Science 1993. 259: 17391742.
  • 48
    Meazza, R., Comes, A., Orengo, A. M., Ferrini, S. and Accolla, R. S., Tumor rejection by gene transfer of the MHC class II transactivator in murine mammary adenocarcinoma cells. Eur. J. Immunol. 2003. 33: 11831192.