Restriction of the T-cell repertoire in tumor-infiltrating lymphocytes from nine patients with renal-cell carcinoma. Relevance of the CDR3 length analysis for the identification of in situ clonal T-cell expansions.
Renal-cell carcinoma (RCC) is one of the human cancers which respond best to immunotherapy. To better characterize the mechanism of the immune response in RCC, we analyzed the T-cell receptor (TCR) beta-chain repertoire in primary RCC, metastases and paired peripheral blood lymphocytes (PBL) from 9 patients. For 3 of these, we analyzed T cells recovered from normal kidney, or from tumor-involved lymph nodes as well as tumor-infiltrating lymphocytes (TIL) expanded in vitro for adoptive immunotherapy. The initial semi-quantitative RT-PCR method for definition of the Vbeta gene usage was not informative enough to distinguish intratumoral clonal T-cell expansions. In contrast, the length pattern analysis of the complementary determining regions 3 (CDR3) allowed oligoclonal T-cell populations to be detected in fresh TIL form the 9 patients with RCC. Furthermore, these oligoclonal TIL populations were not present in normal renal tissue, autologous PBL or tumor-involved lymph nodes. Different clonal T-cell expansions were identified in the primary tumor and in a pulmonary metastasis from the same patient. The detection of clonal T-cell populations observed in RCC suggests an in situ expansion in response to potential tumor antigens. This report provides an overall and accurate description of the T-cell repertoire in a significant number of samples from patients with RCC.
Puisieux
I
I
Department de Biologie des Tumeurs, Centre Leon Berard, Lyon, France.
Bain
C
C
Merrouche
Y
Y
Malacher
P
P
Kourilsky
P
P
Even
J
J
Favrot
M
M
D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000628:therapy; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000276:immunology* / Q000628:therapy; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*
D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta