In Vivo Local Expansion of Clonal T Cell Subpopulations in Renal Cell Carcinoma1

Abstract

Renal cell carcinoma (RCC) is one human tumor to which the immune response may control the growth of tumor cells. These tumors are infil trated by a large mononuclear infiltrate mainly composed of T lympho cytes. To characterize the lymphocytes infiltrating RCC, we analyzed the molecular structure of the T cell receptor (TCR) a and ßchains in tumor and paired peripheral blood lymphocytes from a series of 6 untreated patients. We first determined Va and Vßgene segment usage by PCR using a panel of V specific oligonucleotide primers (Val-w29 and V/ÌIw24). A highly diverse usage of TCR Va and Vßgene usage was observed in 5 of 6 tumors. In addition, the few tumor overexpressed Vßspecificities detected by reverse transcription-PCR were shown to contain minor T cell expansions. Strikingly, 1 of the 6 tumor studied displayed a skewed TCR repertoire with Vß4transcript representing 25% of the TCR signals. Clonality of the tumor overexpressed Vßtranscripts was analyzed by CDR3 size distribution analysis. In the particular tumor displaying a biased repertoire large expansions of T cell subpopulations were detected (particularly in Vß4)specifically at the tumor site. Such T cells may be expanded locally in response to tumor antigens. antibody-like structure. CDR regions 1, 2, and 3 have accordingly been defined for TCR molecules (11). CDR3 regions are encoded by the hypervariable V-J or V-D-J junctions and are essential for binding to the antigenic peptide. The expression of unique rearranged TCR gene products determines the specificity of a given T cell (12). Identification of recurrent TCR transcripts (same CDR3) in T cell populations indicates antigen driven expansion of the corresponding T cells. Thus, the direct analysis of the molecular structure of TCR polypeptides expressed by TIL is one way to study how tumor cells modulate the T cell repertoire. Using different PCR approaches, we analyzed in situ the fine molecular structure of TCR a and ßchains in TIL and paired PBL from 6 RCC patients. A highly diverse repertoire was found in 5 of 6 tumors, whereas it was strongly skewed in the last tumor. Dramatic clonal expansions of few T cell subsets were indeed identified in the last patient. Such data strengthen the view that antigen driven T cell expansion may occur locally and contribute to the control of the tumor evolution at least in some RCC.

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Cite this paper

@inproceedings{Gaudin2006InVL, title={In Vivo Local Expansion of Clonal T Cell Subpopulations in Renal Cell Carcinoma1}, author={Catherine F. M. Gaudin and P. Y. Dietrich and Sylvie Robache and Maryvonne Guillar{\~A} and Bernard J Escudier and M P Lacombe and Anil Kumar and Anne Caignard}, year={2006} }