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ISSN 打印: 1040-8401
ISSN 在线: 2162-6472

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DOI: 10.1615/CritRevImmunol.v18.i1-2.90
pages 77-86

Tumor-Specific Immune Response: Current In Vitro Analyses May Not Reflect the In Vivo Immune Status

Florence Faure
Biologie Moleculaire du Gene, U.277 INSERM, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris, cedex 15, France; lnstitut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif cedex, France
Jos Even
Biologie Moleculaire du Gene, U.277 INSERM, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris, cedex 15, France
Philippe Kourilsky
Biologie Moleculaire du Gene, U.277 INSERM, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris, cedex 15, France

ABSTRACT

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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