Identification of multiple antigens recognized by tumor-infiltrating lymphocytes from a single patient: tumor escape by antigen loss and loss of MHC expression.
The authors describe a patient who experienced recurrence of metastatic melanoma after an initial dramatic response to immunotherapy using peptides derived from gp100, MART-1, and tyrosinase emulsified in incomplete Freund's adjuvant, and present data to support the hypothesis that the progression of disease in this patient was due to in vivo immunoselection for immunoresistant tumor variants. The authors previously demonstrated the existence of T-cell clones in this patient's peripheral blood and tumor-infiltrating lymphocytes (TILs) reactive against multiple antigens, including gp100, the tyrosinase-related protein (TRP)-2, a novel TRP-2 isoform-TRP-2-6b, SOX10, and the melanoma antigen NY-ESO-1. In addition to the multiple HLA-A2 restricted T-cell clones, the authors have now identified additional HLA-B/C-restricted as well as class II (HLA-DP)-restricted anti-melanoma antigen T-cell clones from this patient's TIL. One recurrent tumor showed loss of expression of multiple tumor antigens but retention of HLA class I expression. The other recurrent lesion showed total loss of HLA class I expression even though the tumor cells still expressed many melanoma antigens. This paper thus provides evidence for both the effectiveness of the immune destruction of cancer as well as problems associated with antigen-loss tumor escape mechanisms.
Khong
Hung T
HT
Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1502, USA.
Wang
Qiong J
QJ
Rosenberg
Steven A
SA
D000951:Antigens, Neoplasm / Q000737:chemistry*; D001483:Base Sequence; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D019746:Intramolecular Oxidoreductases / Q000737:chemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000737:chemistry* / Q000276:immunology; D058965:MART-1 Antigen; D008285:Major Histocompatibility Complex; D008545:Melanoma / Q000276:immunology; D008562:Membrane Glycoproteins / Q000737:chemistry; D008875:Middle Aged; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000737:chemistry; D009154:Mutation; D009363:Neoplasm Proteins / Q000737:chemistry; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058951:gp100 Melanoma Antigen
D000951:Antigens, Neoplasm; D016207:Cytokines; D018076:DNA, Complementary; D058965:MART-1 Antigen; C548667:MLANA protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D058951:gp100 Melanoma Antigen; D014442:Monophenol Monooxygenase; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase