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

✍ Scribed by Eric Angevin; Florence Kremer; Catherine Gaudin; Thierry Hercend; Frédéric Triebel

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: French
• Weight: 208 KB
• Volume: 72
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19970729)72:3<431::aid-ijc10>3.0.co;2-f

✦ Synopsis

We assessed the naturally occurring T-cell immune response in primary renal cell carcinoma (RCC) tumors from 12 unselected patients. A predominance of CD3 1 T-cell receptor (TCR)a/b 1 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 1 and HLA-DR 1 and a low percentage of CD25 1 and CD71 1 TILs. The lymphocyte activation gene-3 (LAG-3) was detected in some TIL subpopulations and especially in one patient in whom TILs were predominantly TCRa/b 1 CD8 1 DR 1 LAG-3 1 . In addition, we found that RCC TILs are polarized to a global type 1-like (Th1/Tc1) differentiation pattern (strong secretion of interferon-g 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 Vb 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 Vb1 subpopulation (5% of TCR a/b 1 cells) corresponding to 2 distinct Vb1-Jb1.6 and Vb1-Jb2.3 tumorspecific MHC class I-restricted cytotoxic T lymphocytes supports the view that discrete T-cell subsets contribute readily to in situ immunosurveillance.