Comprehensive analysis of the frequency of recognition of melanoma-associated antigen (MAA) by CD8 melanoma infiltrating lymphocytes (TIL): implications for immunotherapy

Fifty-nine tumor-infiltrating lymphocyte (TIL) cultures established from me lanoma-invaded lymph nodes were screened for recognition of 28 melanoma-ass ociated antigens (MAA) in association with 31 HLA molecules. Twenty-three ( 39%) TIL lines reacted to at least one melanoma antigen. Melanosomal protei ns were recognized by 19 TIL populations and the most prominent responses a gainst these proteins were directed against Melan-A/MART-1 (mainly in assoc iation with HLA-A*0201) and gp100 (in association with diverse HLA contexts ). Ten TIL populations reacted against 10 tumor-specific antigens, in assoc iation with 8 different HLA molecules. HLA-A*0201 and B*3501-restricted res ponses were the most frequent with, respectively, 17 and 7 responses direct ed against 5 distinct antigens. Unexpectedly, the recognition by TIL of dif ferent MAA was frequently restricted by a single HLA in individual tumors, and there was no evidence for the existence of dominant MAA epitopes betwee n tumors, except for Melan-A/MART-1 antigen. This analysis also led to the detection of 21 new HLA-peptide complexes recognized by melanoma TIL. This study, which is to our knowledge the most comprehensive analysis of TIL spe cificity to tumor antigens, has several implications for the design of immu notherapeutic strategies based on immunization against selected tumor epito pes.