Natural T cell immunity against cancer.
It has long been a matter of debate whether tumors are spontaneously immunogenic in patients. With the availability of sensitive methods, naturally occurring T cells directed against tumor-associated antigens (TAAs) can be frequently detected in cancer patients. In this review, we summarize the current data on T cell responses to TAAs in various malignancies, including melanoma, colorectal cancer, leukemia, and breast cancer. T cell responses against various antigens, including melanoma differentiation antigens, carcinoembryonic antigen, epithelial cell adhesion molecule, her-2/neu, Wilms' tumor protein, proteinase 3, NY-ESO-1, and surviving, have been reported in a substantial number of patients. In contrast, other TAAs, including most antigens of the MAGE family, do not usually elicit spontaneous T cell responses. A distinction between direct ex vivo T cell responses and in vitro-generated T cell responses is provided because in vitro stimulation results in quantitative and functional changes of T cell responses. The possible role of TAA-specific T cells in immunosurveillance and tumor escape and the implications for immunological treatment strategies are discussed. Naturally occurring T cells against TAAs are a common phenomenon in tumor patients. Understanding the mechanisms and behavior of natural TAA-specific T cells could provide crucial information for rational development of more efficient T cell-directed immunotherapy.
Nagorsen
Dirk
D
Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, NIH, Bethesda, Maryland 20892, USA.
Scheibenbogen
Carmen
C
Marincola
Francesco M
FM
Letsch
Anne
A
Keilholz
Ulrich
U
D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules