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.