In situ T-cell responses in a primary regressive melanoma and subsequent metastases: A comparative analysis

Abstract

In an earlier study of the immune response in a patient with a cutaneous primary regressive melanoma, a T-cell-receptor diversity analysis demonstrated in situ amplification of certain lymphocytes. Two of them could be cloned and characterized as CD8+ HLA-class-I-restricted CTL with strong selective anti-tumor activity. Following a disease-free period of 3 years, the patient developed a gastric metastasis and subsequently (after an additional year) a metastasis in one axillary lymph node. Melanoma cell lines derived from the 2 secondary lesions have been established here. It was found that these metastatic cells have maintained expression of both HLA-class-I molecules and the peptidic antigen(s) recognized by the 2 clones amplified at the primary site. However, the corresponding T lymphocytes were either undetectable or poorly represented both in the gastric and in the axillary lesions. These results suggest that substantial alterations in the quality of T-cell infiltrates occurred during melanoma progression, despite an apparent stability in presentation of tumor-associated antigen(s) which initially triggered a positive rejection response.