Journal article
T-Cell Receptor Repertoire in Tumor-Infiltrating Lymphocytes. Analysis of Melanoma-Specific Long-Term Lines
Journal of immunotherapy (1997), Vol.16(2), pp.85-94
08/1994
DOI: 10.1097/00002371-199408000-00002
PMID: 7804531
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 (Vαl, 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. © 1994 Raven Press, Ltd.
Details
- Title: Subtitle
- T-Cell Receptor Repertoire in Tumor-Infiltrating Lymphocytes. Analysis of Melanoma-Specific Long-Term Lines
- Creators
- Michael I. Nishimura - California Institute of TechnologyYutaka Kawakami - Cell Signaling TechnologyPatrick Charmley - California Institute of TechnologyBert OʼNeilJoel Shilyansky - National Institutes of HealthJohn R. Yannelli - National Institutes of HealthSteven A. Rosenberg - National Institutes of HealthLeroy Hood - California Institute of Technology
- Resource Type
- Journal article
- Publication Details
- Journal of immunotherapy (1997), Vol.16(2), pp.85-94
- DOI
- 10.1097/00002371-199408000-00002
- PMID
- 7804531
- ISSN
- 1524-9557
- eISSN
- 1537-4513
- Language
- English
- Date published
- 08/1994
- Academic Unit
- Stead Family Department of Pediatrics; Surgery
- Record Identifier
- 9984322935002771
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