T-cell receptor repertoire in tumor-infiltrating lymphocytes. Analysis of melanoma-specific long-term lines

M. I. Nishimura, Yutaka Kawakami, P. Charmley, B. O'Neil, J. Shilyansky, J. R. Yannelli, S. A. Rosenberg, L. Hood

Research output: Contribution to journalArticle

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Abstract

Cytotoxic T-lymphocytes (CTLs) can be isolated from human melanoma biopsies that specifically lyse autologous melanoma in vitro and can be effective therapeutic agents for patients with advanced disease. Recent evidence indicates that HLA-A2-restricted, melanoma-specific tumor- infiltrating lymphocytes (TILs) recognize melanomas obtained from different HLA-A2+ patients, suggesting the presence of one or more common melanoma antigens. Furthermore, T-cell receptor (TCR) repertoire analysis by other groups of TILs from fresh melanoma biopsies suggests that there is limited TCR V gene usage in TILs. One serious limitation in analyzing the TCR repertoire in fresh tumors has been the inability to correlate TCR usage with immune function. Therefore, the TCR repertoire was determined in long-term TIL cultures that specifically lysed autologous melanoma in vitro and in many cases mediated in vivo regression of metastatic cancer in patients with advanced disease. The TCR repertoire in cultured melanoma-specific TILs was diverse, with each TIL containing an average of 9.5 ± 5.7 of the 23 Vα and 11.2 ± 5.9 of the 23 Vβ subfamilies. Despite the large diversity observed, several Vα and Vβ genes (Vα1, Vα2, Vα22, Vβ13, Vβ14, and Vβ18) are very commonly found in melanoma-specific TILs. No statistically significant associations were observed between the presence of a TCR V gene subfamily in TILs and clinical response, HLA haplotype, or age of the culture. Even though the results in this study suggest that certain TCR V gene segments may be involved in immune responses to human melanoma, we were unable to demonstrate functionally that a particular T-cell clonotype recognizes melanoma tumor- associated antigens. Only the analysis of melanoma-specific CTL clones can determine which clonotypes are important in lysis of human melanoma.

Original languageEnglish
Pages (from-to)85-94
Number of pages10
JournalJournal of Immunotherapy
Volume16
Issue number2
Publication statusPublished - 1994
Externally publishedYes

Fingerprint

Tumor-Infiltrating Lymphocytes
T-Cell Antigen Receptor
Melanoma
T-Cell Receptor Genes
Melanoma-Specific Antigens
HLA-A2 Antigen
Cytotoxic T-Lymphocytes
Biopsy
Proxy
Neoplasm Antigens
Haplotypes
Neoplasms
Clone Cells

Keywords

  • Melanoma
  • T-Cell receptor
  • Tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Pharmacology

Cite this

Nishimura, M. I., Kawakami, Y., Charmley, P., O'Neil, B., Shilyansky, J., Yannelli, J. R., ... Hood, L. (1994). T-cell receptor repertoire in tumor-infiltrating lymphocytes. Analysis of melanoma-specific long-term lines. Journal of Immunotherapy, 16(2), 85-94.

T-cell receptor repertoire in tumor-infiltrating lymphocytes. Analysis of melanoma-specific long-term lines. / Nishimura, M. I.; Kawakami, Yutaka; Charmley, P.; O'Neil, B.; Shilyansky, J.; Yannelli, J. R.; Rosenberg, S. A.; Hood, L.

In: Journal of Immunotherapy, Vol. 16, No. 2, 1994, p. 85-94.

Research output: Contribution to journalArticle

Nishimura, MI, Kawakami, Y, Charmley, P, O'Neil, B, Shilyansky, J, Yannelli, JR, Rosenberg, SA & Hood, L 1994, 'T-cell receptor repertoire in tumor-infiltrating lymphocytes. Analysis of melanoma-specific long-term lines', Journal of Immunotherapy, vol. 16, no. 2, pp. 85-94.
Nishimura MI, Kawakami Y, Charmley P, O'Neil B, Shilyansky J, Yannelli JR et al. T-cell receptor repertoire in tumor-infiltrating lymphocytes. Analysis of melanoma-specific long-term lines. Journal of Immunotherapy. 1994;16(2):85-94.
Nishimura, M. I. ; Kawakami, Yutaka ; Charmley, P. ; O'Neil, B. ; Shilyansky, J. ; Yannelli, J. R. ; Rosenberg, S. A. ; Hood, L. / T-cell receptor repertoire in tumor-infiltrating lymphocytes. Analysis of melanoma-specific long-term lines. In: Journal of Immunotherapy. 1994 ; Vol. 16, No. 2. pp. 85-94.
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