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

Int J Cancer. 1996 Apr 10;66(2):201-8. doi: 10.1002/(SICI)1097-0215(19960410)66:2<201::AID-IJC11>3.0.CO;2-F.

Abstract

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.

MeSH terms

  • Carcinoma, Renal Cell / immunology*
  • Carcinoma, Renal Cell / therapy
  • Humans
  • Immunotherapy, Adoptive
  • Interleukin-2 / therapeutic use
  • Kidney Neoplasms / immunology*
  • Kidney Neoplasms / therapy
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • T-Lymphocytes / immunology*

Substances

  • Interleukin-2
  • Receptors, Antigen, T-Cell, alpha-beta