Immunologic Nonresponsiveness to Tumors

Over the past several years it has become clear that malignant cells express a variety of tumor associated antigens, and T cells reactive to these antigens have been identified. However, the T cells are not effective in rejecting tumors. In general, T cells that are not tolerized within the thymus have the potential to be rendered tolerant by one of three mechanisms. Immune deviation occurs when regulatory T cells which share a common precursor differentiate away from the phenotype required to effect a particular immune response. Anergy induction occurs when a T cell is stimulated through its T cell receptor in the absence of costimulation. Activation-induced cell death (AICD) is apoptosis of activated T cells upon subsequent encounter with antigen. There is emerging information that some of these mechanisms can be responsible for the lack of T cell responsiveness to tumor cells. Also, tumor cells can acquire attributes that interfere with an immune response, including down-regulation of MHC molecules or other molecules involved in antigen processing; secretion of the immunosuppressive cytokine TGFbeta; and expression of the apoptosis-inducing surface molecule, Fas ligand. An expansion in our understanding of how tumor cells evade a T cell mediated death will provide insight into potential strategies to improve immunotherapeutic approaches to cancer patients.