Targets of protective tumor immunity.
The identification of antigens associated with tumor destruction is a major goal of cancer immunology. Several genetic and biochemical techniques have revealed a broad range of gene products that elicit immune recognition in cancer patients, but the biologic importance of these responses in most cases is poorly understood. While some targets are linked to tumor regressions in the context of adoptive cellular therapies or cancer vaccinations, the possible roles of immunity to most antigens in disease pathogenesis and clinical outcomes remain to be elucidated. One strategy for characterizing antigens that elicit clinically significant immune recognition involves the study of patients who achieve durable clinical benefits from immune treatments. Through this approach, we uncovered the immunogenicity of major histocompatibility chain-related protein A (MICA), which is a ligand for NKG2D, and ERp5, a protein disulfide isomerase involved in MICA shedding. Our findings suggest that components of the NKG2D pathway may be attractive targets for therapeutic monoclonal antibodies.
Dranoff
Glenn
G
Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Institute, Boston, MA 02115, USA. glenn_dranoff@dfci.harvard.edu
D000917:Antibody Formation; D015703:Antigens, CD / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D039481:CD11b Antigen / Q000276:immunology; D060908:CTLA-4 Antigen; D019496:Cancer Vaccines / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007109:Immunity; D007111:Immunity, Cellular; D007165:Immunosuppression Therapy / Q000379:methods; D007167:Immunotherapy / Q000379:methods; D008545:Melanoma / Q000235:genetics / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D019704:Protein Disulfide-Isomerases / Q000276:immunology
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D039481:CD11b Antigen; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D019496:Cancer Vaccines; C509295:ITGAM protein, human; C496931:PDIA6 protein, human; D019704:Protein Disulfide-Isomerases