SELECTIVE ACCUMULATION OF T-CELLS ACCORDING TO T-CELL RECEPTOR V-BETAGENE USAGE IN SKIN-CANCER

To investigate whether specific T-cell populations are overrepresented in tumor-infiltrating lymphocytes (TIL) in skin cancer, we determined the T-cell receptor (TCR) diversity in biopsy specimens of basal cell carcinoma and squamous cell carcinoma. Immunostaining of tissue secti ons indicated that the majority of T cells expressed alpha beta TCRs. To assess diversity of the TCR beta chain, RNA was isolated directly f rom the tumor specimens and peripheral blood mononuclear cells (PBMC) from the same patient, cDNA was synthesized, and variable (V) beta cha in gene usage was determined by the polymerase chain reaction (PCR). I n each basal cell (n = 11) and squamous cell (n = 7) cinema studied, s everal V beta families were overrepresented in TIL versus PBMC, in tha t they accounted for greater than 5% of the repertoire in TIL and were at least 2% higher in TIL than in PBMC. The predominant V beta gene s egments overrepresented in TIL generally differed from individual to i ndividual. Simultaneous comparison of the V beta repertoire of TIL to that of uninvolved skin and PBMC from the same individual revealed pre ferential expression of V beta families within the TIL in three of fiv e basal cell and four of four squamous cell carcinomas. Again, the pre dominant V beta s differed from individual to individual. Comparison o f the TCR repertoire in uninvolved skin versus PBMC did indicate that some V beta families were overexpressed in the resident T-cell compart ment in skin, although the overrepresented families were not constant from individual to individual. These data indicate the selective conce ntration of T cells bearing specific alpha beta TCRs in the local immu ne response to basal cell and squamous cell carcinomas.