Comprehensive analysis of the frequency of recognition of melanoma-associated antigen (MAA) by CD8 melanoma infiltrating lymphocytes (TIL): implications for immunotherapy
H. Benlalam et al., Comprehensive analysis of the frequency of recognition of melanoma-associated antigen (MAA) by CD8 melanoma infiltrating lymphocytes (TIL): implications for immunotherapy, EUR J IMMUN, 31(7), 2001, pp. 2007-2015
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.