Melanoma antigen recognition by tumour‐infiltrating T lymphocytes (TIL): effect of differential expression of Melan‐A/MART‐1

• Published in: Clinical and experimental immunology Vol. 119; no. 1; pp. 11 - 18
• Main Authors: Ramirez‐Montagut, T., Andrews, D. M., Ihara, A., Pervaiz, S., Pandolfi, F., Van Den Elsen, P. J., Waitkus, R., Boyle, L. A., Hishii, M., Kurnick, J. T.
• Format: Journal Article
• Language: English
• Published: Oxford BSL Blackwell Science Ltd 01.01.2000; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: Amino Acid Sequence; Antigens, Neoplasm - genetics; Base Sequence; Biological and medical sciences; Cancer Immunology; Clone Cells; cytotoxic T lymphocytes; Cytotoxicity, Immunologic; DNA - genetics; Gene Expression; Host-tumor relations. Immunology. Biological markers; Humans; Lymphocytes, Tumor-Infiltrating - immunology; MART-1 Antigen; Medical sciences; melanoma; Melanoma - genetics; Melanoma - immunology; Melan‐A/MART‐1; Molecular Sequence Data; Neoplasm Proteins - genetics; Neoplasm Proteins - immunology; PCR‐SSCP; Phenotype; Polymorphism, Single-Stranded Conformational; Receptors, Antigen, T-Cell, alpha-beta - genetics; T cell receptor; Tumor Cells, Cultured; Tumors; tumour‐infiltrating lymphocytes; Human; Immune response; Tumor associated antigen; Antigenic determinant; T-Lymphocyte; Malignant melanoma; Cytotoxicity; Cellular immunity; Malignant tumor
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.2000.01089.x

We have isolated, from an individual patient with metastatic melanoma, a series of eight TIL clones capable of lysing autologous melanoma cell targets. Six of the eight clones expressed TCRAV2S1 and lysed targets expressing HLA‐A2 and the Melan‐A/MART‐1 peptide: AAGIGILTV. Polymerase chain reaction‐single stranded conformational polymorphism (PCR‐SSCP) analysis showed that the Melan‐A/MART‐1‐specific clones were predominant in the bulk culture prior to cloning. However, the tumour progressed in vivo even in the presence of these tumour cell‐lytic clones. Using the anti‐Melan‐A/MART‐1 MoAb (A‐103), we noted that Melan‐A/MART‐1 expression on three melanoma cell lines varied considerably during in vitro culture, in the absence of T cell immunoselection, relative to cell density. Tumour cells which spontaneously decreased Melan‐A/MART‐1 expression were less susceptible to specific TIL lysis. Melan‐A/MART‐1 expression and susceptibility to lysis increased in cells cultured at lower density. These data suggest that modulation of tumour antigen may account for tumour progression in the presence of tumour cell‐lytic T lymphocytes. The observations suggest a possible explanation for the common finding of Melan‐A/MART‐1‐specific lytic TIL in clinically progressing melanomas, as well as a possible pathway for therapeutic intervention.