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The Apoptosis Inhibitor Protein Survivin Induces Tumor-specific CD8⁺ and CD4⁺ T Cells in Colorectal Cancer Patients¹

Units of Immunotherapy of Human Tumors [C. Casa., P. Da., L. R., P. De., F. R., G. P., C. Cast.], Colorectal Surgery [G. G., F. B., E. L.], Molecular Therapy [D. M.], and Determinants of Response to Prognosis and Treatment [A. C.], and Department of Pathology [S. A.], Istituto Nazionale per lo Studio e la Cura dei Tumori, 20133 Milan, Italy

The identification of tumor-associated antigens expressed by colorectal carcinoma remains one of the major goals for designing novel immunological treatments for this tumor. By using a reverse-immunology approach, we show here that the inhibitor of apoptosis protein, survivin, is immunogenic in colorectal cancer patients. In particular, we found that survivin elicited CD8⁺ T cell-mediated responses in peripheral blood or in tumor-associated lymphocytes from patients at different disease stage. Colorectal carcinoma cells were recognized by survivin-specific T lymphocytes, and the survivin-specific, class-I HLA-restricted T lymphocytes were fully activated and released interleukin-2 in response to HLA/survivin-peptide complexes expressed by tumor cells. In addition to CD8-mediated responses, survivin specifically stimulated CD4⁺ T-cell reactivity in peripheral blood lymphocytes from the same patients, thus suggesting that a complete activation of the immune system may occur in response to this antiapoptotic protein. These findings indicate that survivin could be considered a valuable tumor-associated antigen for immune-based clinical approaches in colorectal cancer.

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