Antigen-driven T-cell selection in patients with cervical cancer as evidenced by T-cell receptor analysis and recognition of autologous tumor.

We characterized the T-cell receptor (TCR) repertoire in freshly harvested tumor lesions, in short-term-expanded CD4(+) tumor infiltrating lymphocytes (TIL) as well as in CD4(+) and CD8(+) peripheral blood lymphocytes (PBL) from three patients with cervical cancer. Skewing of the T-cell repertoire as defined by measuring the length of the complementarity-determining region 3 (CDR3) of the TCR VA and VB chains was observed in CD8(+) PBL, in freshly harvested tumor tissue, as well as in CD4(+) TIL. Comparative analysis of the TCR repertoire revealed unique monoclonal TCR transcripts within the tumor lesion which were not present in PBL, suggesting selection of TCR clonotypes due to antigenic stimulation. TCR repertoire analysis of the short-term (7-day) CD4(+) TIL lines revealed that the TCR composition is markedly different from that in CD4(+) PBL or in the freshly harvested tumor tissue. Only one-third of CD4(+) TIL lines showed HLA-DR-restricted recognition of autologous tumor cells as defined by cytolysis. These data provide support for the antigen-driven selection of T cells within cervical cancer lesions and suggest that analysis of the TCR repertoire may aid in obtaining an objective description of the immune response in patients with cervical cancer who are undergoing epitope-based immunotherapy.