Cytotoxic T lymphocytes: role in immunosurveillance and in immunotherapy

Experiments in mice and recent human clinical studies have clearly shown the contribution of CD8+ T lymphocyte in the control of tumor development. CD8+ T lymphocytes are a constitutive component of the immune response during the development of cancer. In murine models, the efficiency of various cancer vaccines mainly depends on their ability to induce CD8+ T lymphocytes. Clinical responses in immunotherapy treated cancer patients have been associated with the presence of antitumor specific CD8+ T lymphocytes. In spontaneous regressive melanomas, intratumor antigen specific CD8+ cytotoxic T cells were expanded suggesting their involvement in the tumor shrinkage. Administration of antitumor specific cytotoxic T clones in mice resulted in antitumor responses which directly demonstrated the therapeutic efficiency of these cells. However, in most cases during cancer progression, the presence of antitumor CD8 T lymphocyte is not associated with clinical responses. Intrinsic functional abnormalities of these cells or a defect of CD8+ T cell migration to the tumor may in part explain their failure to inhibit tumor development. On the other hand, tumors also develop immune escape mechanisms (down modulation of tumor antigens, secretion of immunosuppressive factors, expression of anti-apoptotic molecules by the tumors, or pro-apoptotic factors inducing T cell death) to resist to the CD8+ T cell attack. To circumvent these tumor escape mechanisms, efficient cancer vaccines will have to recruit CD8+ T cells associated with other immune effectors.