In vivo Accumulation of the Same Anti-Melanoma T Cell Clone in Two Different Metastatic Sites

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 94; no. 4; pp. 1378 - 1383
• Main Authors: Hishii, Makoto, Andrews, David, Boyle, Lenora A., Wong, Johnson T., Pandolfi, Franco, Van Den Elsen, Peter J., Kurnick, James T.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 18.02.1997; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences of the USA
• Subjects: Abdomen - pathology; Aged; Biological Sciences; Cell Line; Cell lines; Clone Cells - immunology; Humans; Immunity (Disease); Lesions; Leukocytes; Lymphocytes, Tumor-Infiltrating - cytology; Lymphocytes, Tumor-Infiltrating - immunology; Male; Melanoma; Melanoma - immunology; Melanoma - secondary; Molecular Sequence Data; Neoplasm Metastasis; Polymerase chain reaction; Polymorphism, Single-Stranded Conformational; Receptors, Antigen, T-Cell, alpha-beta - genetics; RNA; Sequence Analysis, DNA; Shoulder - pathology; Single stranded conformational polymorphism; Skin Neoplasms - immunology; Skin Neoplasms - secondary; T cell antigen receptors; T lymphocytes; T-Lymphocytes, Cytotoxic - immunology; Tissue culture techniques; Tumor Cells, Cultured; Tumors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.94.4.1378

In a patient with progressing metastatic melanoma, we showed that the same autologous tumorcytolytic CD8+ tumor infiltrating lymphocyte (TIL) clone accumulated in two separate metastatic sites. This clone, which represented three of eight independently derived clones from a tumor deposit on the skin of the abdomen, also represented two of eight clones derived from a skin lesion on the shoulder. This clone could be identified by its use of a unique TCRBV2-nD1n-J1S6 sequence, and could also be detected by single-stranded conformational polymorphism (SSCP) as the dominant TCRBV2-expressing clone among CD8+ TILs propagated from both shoulder and abdominal lesions. Using SSCP analysis, we also demonstrated that this clone was dominant in the fresh tumor tissue and in all TILs in which CD8+ were strongly represented, including several separate but parallel cultures. The SSCP pattern for this clone was not apparent among CD4+ TILs or CD8+ peripheral blood mononuclear cells. The SSCP analysis of the tumor tissue prior to in vitro culture is an indication that the selection for this anti-tumor cytotoxic T cell clone was a reflection of its in vivo accumulation. Thus, we provide evidence that melanomas are immunogenic and able to select for cytotoxic antitumor-specific TIL clones that are expanded in vivo and can circulate to accumulate in different tumor sites. However, because these clones were isolated from progressing tumor metastases, the accumulation of these specific cytotoxic T cells was not sufficient to contain tumor growth.