Melanoma antigen recognition by tumour-infiltrating T lymphocytes (TIL): effect of differential expression of Melan-A/MART-1

We have isolated, from an individual patient with metastatic melanoma, a se ries of eight TIL clones capable of lysing autologous melanoma cell targets . Six of the eight clones expressed TCRAV2S1 and lysed targets expressing H LA-A2 and the Melan-A/MART-1 peptide: AAGIGILTV. Polymerase chain reaction- single stranded conformational polymorphism (PCR-SSCP) analysis showed that the Melan-A/MART-1-specific clones were predominant in the bulk culture pr ior to cloning. However, the tumour progressed in vivo even in the presence of these tumour cell-lytic clones. Using the anti-Melan-A/MART-1 MoAb (A-1 03), we noted that Melan-A/MART-1 expression on three melanoma cell lines v aried considerably during in vitro culture, in the absence of T cell immuno selection, relative to cell density. Tumour cells which spontaneously decre ased Melan-A/MART-1 expression were less susceptible to specific TIL lysis. Melan-A/MART-1 expression and susceptibility to lysis increased in cells c ultured at lower density. These data suggest that modulation of tumour anti gen may account for tumour progression in the presence of tumour cell-lytic T lymphocytes. The observations suggest a possible explanation for the com mon finding of Melan-A/MART-1-specific lytic TIL in clinically progressing melanomas, as well as a possible pathway for therapeutic intervention.