Analysis of T-cell immune response in renal cell carcinoma: polarization to type 1-like differentiation pattern, clonal T-cell expansion and tumor-specific cytotoxicity

Int J Cancer. 1997 Jul 29;72(3):431-40. doi: 10.1002/(sici)1097-0215(19970729)72:3<431::aid-ijc10>3.0.co;2-f.

Abstract

We assessed the naturally occurring T-cell immune response in primary renal cell carcinoma (RCC) tumors from 12 unselected patients. A predominance of CD3+ T-cell receptor (TCR)alpha/beta+ T cells was observed in tumor-infiltrating lymphocytes (TILs), in contrast with peripheral blood lymphopenia found in some patients. Activation antigen expression on TILs revealed an imbalance in the activation status, with a significant percentage of CD69+ and HLA-DR+ and a low percentage of CD25+ and CD71+ TILs. The lymphocyte activation gene-3 (LAG-3) was detected in some TIL subpopulations and especially in one patient in whom TILs were predominantly TCR alpha/beta+CD8+DR+LAG-3+. In addition, we found that RCC TILs are polarized to a global type 1-like (Th1/Tc1) differentiation pattern (strong secretion of interferon-gamma and interleukin-2 (IL-2) following CD3/TCR crosslinking) but are under the influence of the down-modulatory cytokines IL-6 (secreted by tumor cells) and IL-10, within the tumor microenvironment. In 3 of 5 patients, clonal T-cell expansion at the tumor site was found for several Vbeta specificities, suggesting that in situ stimulation of specific clonotypes in response to potential tumor antigens is a frequent event in RCC. Furthermore, in one patient, selective intratumor amplification of a Vbeta1 subpopulation (5% of TCR alpha/beta+ cells) corresponding to 2 distinct Vbeta1-Jbeta1.6 and Vbeta1-Jbeta2.3 tumor-specific MHC class I-restricted cytotoxic T lymphocytes supports the view that discrete T-cell subsets contribute readily to in situ immunosurveillance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD / analysis
  • Carcinoma, Renal Cell / immunology*
  • Cell Differentiation
  • Clone Cells
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic*
  • Female
  • Humans
  • Kidney Neoplasms / immunology*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Male
  • Middle Aged
  • Phenotype
  • Receptors, Antigen, T-Cell / physiology
  • Signal Transduction
  • T-Lymphocytes / immunology*
  • Tumor Cells, Cultured

Substances

  • Antigens, CD
  • Cytokines
  • Receptors, Antigen, T-Cell