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Clinical Cancer Research Vol. 9, 4296-4303, October 1, 2003
© 2003 American Association for Cancer Research

Perspectives

Natural T Cell Immunity against Cancer

Dirk Nagorsen, Carmen Scheibenbogen, Francesco M. Marincola, Anne Letsch and Ulrich Keilholz1

Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, NIH, Bethesda, Maryland 20892 [D. N., F. M. M.], and Medizinische Klinik III, Hematology, Oncology, and Transfusion Medicine, University Hospital Benjamin Franklin, Free University, 12200 Berlin, Germany [C. S., A. L., U. K.]

ABSTRACT

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.




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