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Exuberated Numbers of Tumor-Specific T Cells Result in Tumor Escape

¹ Department of Immunology, Weizmann Institute of Science, Rehovot, Israel and ² Department of Oncology, Hadassah-Hebrew University Hospital, Sharett Institute, Jerusalem, Israel

Requests for reprints: Lea Eisenbach, Weizmann Institute of Science, Department of Immunology, Rehovot POB 26, 76100, Israel. Phone: 972-8-934-4555; Fax: 972-8-934-4141; E-mail: lea.eisenbach{at}weizmann.ac.il.

Key Words: Tumor escape • CTL • antigen silencing

Cytotoxic T cells (CTL) play a major role in tumor rejection. Expansion of CTLs, either by immunization or adoptive transfer, is a prominent goal in current immunotherapy. The antigen-specific nature of these expansion processes inevitably initiates a clonotypic attack on the tumor. By injecting an Ovalbumin-expressing melanoma into OT-I mice, in which >90% of CTLs recognize an Ovalbumin peptide, we show that an increased number of tumor-specific CTLs causes emergence of escape variants. We show that these escape variants are a result of antigen silencing via a yet undetermined epigenetic mechanism, which occurs frequently and is spontaneously reversible. We further show that an increase in the time of tumor onset in OT-I compared with C57BL/6J is a result of immune selection. [Cancer Res 2008;68(9):3450–7]