Immunologic mechanisms of antitumor activity.
The growth and metastatic spread of tumors, to a large extent, depends on their capacity to evade host immune surveillance and overcome host defenses. All tumors express antigens that are recognized to a variable extent by the immune system, but in many cases an inadequate immune response is elicited because of partial antigen masking or ineffective activation of effector cells. Tumor antigens presented in the context of major histocompatability antigen (MHC) class I complexes on either the tumor cell itself or on antigen-presenting cells are capable of inducing tumor-specific cytotoxic T lymphocytes. The presence of costimulatory molecules, such as B7-1 and B7-2, on antigen-presenting cells and the secretion of IL-2 promote the differentiation of recruited CD8+ lymphocytes into cytotoxic T lymphocytes. Tumor escape from immune effectors is most often caused by weak immunogenicity of tumor antigens, antigen masking, or overall immunosuppression, a characteristic of advanced cancer. Failure of antigen processing or binding to MHC molecules, inadequate or low-affinity binding of MHC complexes to T-cell receptors, or inadequate expression of costimulatory adhesion molecules in conjunction with the antigen-presenting MHC complex may all lead to poor immunogenicity of tumor-associated peptides and impaired antitumor response. Therapeutic interventions to augment tumor antigenicity include vaccination with immunogenic peptides, administration of in vitro expanded and activated immune effector cells, in vivo effector cell expansion with cytokine therapies, or genetic modification of either immune effectors or tumor cells with cytokine genes or genes encoding costimulatory molecules to effectively activate the immune response.
Foss
Francine M
FM
Experimental Therapeutics, Tufts New England Medical Center, Boston, MA 02111, USA.
D000818:Animals; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells; D006801:Humans; D016233:Immunotherapy, Active; D016219:Immunotherapy, Adoptive; D007694:Killer Cells, Natural; D008264:Macrophages; D008285:Major Histocompatibility Complex; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory; D022223:Vaccines, Subunit
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D022223:Vaccines, Subunit