每年出版 6 期
ISSN 打印: 1040-8401
ISSN 在线: 2162-6472
Indexed in
Tumor-Specific Immune Response: Current In Vitro Analyses May Not Reflect the In Vivo Immune Status
摘要
Although our knowledge and understanding of tumor-specific cytotoxic T lymphocytes (CTL) have expanded considerably, the long-term work needed to assay CTL has precluded their analysis in large numbers of patients. Moreover, in vitro culture steps may introduce major biases. New approaches to identify tumor-specific CTL clones would be helpful. As a means to describe the in situ immune status by T-cell repertoire analysis, we developed the Immunoscope approach, a PCR-based method that allows us to determine the spectra of CDR3 lengths of the TCR chains displayed by complex populations of T cells. We review here some of our data about melanoma. Tumor-infiltrating lymphocytes of a melanoma patient were analyzed by different means and melanoma-specific T-cell clones were derived. Two categories of tumor-specific CD8+ CTL clones were derived from the infiltrate of a tumor-proximal invaded lymph node. The majority of T-cell clones specifically lyse the autologous tumor cell lines and predominantly recognize the HLA-A2/MART-127.35 peptide complex. The in vivo representativity of such CTL was assessed by the immunoscope technology. Among three MART- 1-specific clones, none was detectable in situ. The other kind of tumor-specific CD8+ CTL did not lyse autologous melanoma cell lines but lysed the “fresh” autologous tumor cells in a MHC class I dependent manner. The immunoscope approach revealed that one of the latter was detectable in situ among tumor-infiltrating lymphocytes although not among PBMC. These data indicate that melanoma-specific lymphocytes that could not have been selected through conventional screening procedures may be important in tumor rejection. Our results suggest that a better characterization of tumor-specific immune responses will be important for the optimization of specific immunotherapy strategies and the long-term follow-up of patients.
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