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

We assessed the naturally occurring T-cell immune response in primary renal cell carcinoma (RCC) tumors from 12 unselected patients, A predo minance of CD3(+) T-ceIl receptor (TCR)alpha/beta(+) T cells was obser ved in tumor-infiltrating lymphocytes (TILs), in contrast with periphe ral blood lymphopenia found in some patients. Activation antigen expre ssion on TILs revealed an imbalance in the activation status, with a s ignificant percentage of CD69(+) and HLA-DR+ and a low percentage of C D25(+) and CD71(+) TILs. The lymphocyte activation gene-3 (LAG-3) was detected in some TIL subpopulations and especially in one patient in w hom TILs were predominantly TCR alpha/beta(+)CD8(+)DR(+)LAG-3(+). In a ddition, we found that RCC TILs are polarized to a global type I-like (Thl/Tcl) differentiation pattern (strong secretion of interferon-gamm a and interleukin-2 (IL-2) following CD3/TCR cross-linking) but are un der the influence of the down-modulatory cytokines IL-6 (secreted by t umor cells) and IL-10, within the tumor microenvironment. In 3 of 5 pa tients, clonal T-cell expansion at the tumor site was found for severa l V beta specificities, suggesting that in situ stimulation of specifi c clonotypes in response to potential tumor antigens is a frequent eve nt in RCC. Furthermore, in one patient, selective intratumor amplifica tion of a V beta I subpopulation (5% of TCR alpha/beta(+) cells) corre sponding to 2 distinct V beta I-J beta 1.6 and V beta 1-J beta 2,3 tum or-specific MHC class I-restricted cytotoxic T lymphocytes supports th e view that discrete T-cell subsets contribute readily to in situ immu nosurveillance. (C) 1997 Wiley-Liss, Inc.