T cell receptor Vβ2 and Vβ6 mediate tumor-specific cytotoxicity by tumor-infiltrating lymphocytes in ovarian cancer

George E. Peoples, Michael Davey, Peter S. Goedegebuure, Deric D. Schoof, Timothy J. Eberlein

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Abstract

The interaction between T lymphocytes and the Ag-HLA complex on tumor cells is mediated by the TCR. The diversity and the specificity of the TCR are in part secondary to the gene rearrangement of the V region on the β-chain (Vβ). To determine whether a restricted number of TCR Vβ genes are utilized in the recognition of ovarian cancer, tumor-infiltrating lymphocytes (TIL) were isolated from six consecutive untreated ovarian cancer patients. TIL were also cultured using repeated autologous tumor stimulation, and by 7 wk, five of six patients produced bulk cultures consisting of >50% CD8+ T cells and demonstrating an autologous tumor-specific pattern of cytotoxicity. TCR Vβ gene usage was analyzed in the five patients yielding fresh TIL and corresponding 7-wk cultured, tumor-specific TIL; 22 primers specific for 20 TCR Vβ gene families were employed and amplified by polymerase chain reaction and then quantitated by HPLC. A hetergeneous pattern of Vβ usage was seen in the fresh TIL; however, Vβ2, Vβ3, Vβ6, Vβ7, Vβ8, and Vβ13.1 were found in increased proportions in at least three of five patients. In the 7-wk tumor-specific TIL, Vβ analysis showed an increased usage of Vβ2 Vβ3, Vβ6, and Vβ7 in more than three of five patients. No significant change in Vβ representation was seen in control populations that were not stimulated with tumor. Looking at the percent change in Vβ usage between fresh and 7-wk tumor-specific cultures, Vβ2 and Vβ6 were augmented significantly in at least three of five patients (108% and 61%, respectively). To verify that the increase in representation of these Vβ families was responsible for the increased cytotoxicity observed, mAb specific for Vβ2 and Vβ6 were used to block tumor lysis. Anti-Vβ6 and anti-Vβ2 significantly blocked cytotoxicity against autologous tumor cells in those TIL populations expressing increased levels of these Vβ families. These data suggest that a selective repertoire of TCR Vβ genes is used to recognize the Ag-HLA class I complexes on the surface of ovarian tumor cells, and specifically Vβ2 and Vβ6 appear to mediate antitumor activity. These findings may aid in the development of a more specific immunotherapy in ovarian cancer.

Original languageEnglish (US)
Pages (from-to)5472-5480
Number of pages9
JournalJournal of Immunology
Volume151
Issue number10
StatePublished - Nov 15 1993

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Tumor-Infiltrating Lymphocytes
T-Cell Antigen Receptor
Ovarian Neoplasms
Neoplasms
Genes
T-Lymphocytes
Gene Rearrangement
Immunotherapy
Population
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Immunology

Cite this

Peoples, G. E., Davey, M., Goedegebuure, P. S., Schoof, D. D., & Eberlein, T. J. (1993). T cell receptor Vβ2 and Vβ6 mediate tumor-specific cytotoxicity by tumor-infiltrating lymphocytes in ovarian cancer. Journal of Immunology, 151(10), 5472-5480.

T cell receptor Vβ2 and Vβ6 mediate tumor-specific cytotoxicity by tumor-infiltrating lymphocytes in ovarian cancer. / Peoples, George E.; Davey, Michael; Goedegebuure, Peter S.; Schoof, Deric D.; Eberlein, Timothy J.

In: Journal of Immunology, Vol. 151, No. 10, 15.11.1993, p. 5472-5480.

Research output: Contribution to journalArticle

Peoples, GE, Davey, M, Goedegebuure, PS, Schoof, DD & Eberlein, TJ 1993, 'T cell receptor Vβ2 and Vβ6 mediate tumor-specific cytotoxicity by tumor-infiltrating lymphocytes in ovarian cancer', Journal of Immunology, vol. 151, no. 10, pp. 5472-5480.
Peoples, George E. ; Davey, Michael ; Goedegebuure, Peter S. ; Schoof, Deric D. ; Eberlein, Timothy J. / T cell receptor Vβ2 and Vβ6 mediate tumor-specific cytotoxicity by tumor-infiltrating lymphocytes in ovarian cancer. In: Journal of Immunology. 1993 ; Vol. 151, No. 10. pp. 5472-5480.
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abstract = "The interaction between T lymphocytes and the Ag-HLA complex on tumor cells is mediated by the TCR. The diversity and the specificity of the TCR are in part secondary to the gene rearrangement of the V region on the β-chain (Vβ). To determine whether a restricted number of TCR Vβ genes are utilized in the recognition of ovarian cancer, tumor-infiltrating lymphocytes (TIL) were isolated from six consecutive untreated ovarian cancer patients. TIL were also cultured using repeated autologous tumor stimulation, and by 7 wk, five of six patients produced bulk cultures consisting of >50{\%} CD8+ T cells and demonstrating an autologous tumor-specific pattern of cytotoxicity. TCR Vβ gene usage was analyzed in the five patients yielding fresh TIL and corresponding 7-wk cultured, tumor-specific TIL; 22 primers specific for 20 TCR Vβ gene families were employed and amplified by polymerase chain reaction and then quantitated by HPLC. A hetergeneous pattern of Vβ usage was seen in the fresh TIL; however, Vβ2, Vβ3, Vβ6, Vβ7, Vβ8, and Vβ13.1 were found in increased proportions in at least three of five patients. In the 7-wk tumor-specific TIL, Vβ analysis showed an increased usage of Vβ2 Vβ3, Vβ6, and Vβ7 in more than three of five patients. No significant change in Vβ representation was seen in control populations that were not stimulated with tumor. Looking at the percent change in Vβ usage between fresh and 7-wk tumor-specific cultures, Vβ2 and Vβ6 were augmented significantly in at least three of five patients (108{\%} and 61{\%}, respectively). To verify that the increase in representation of these Vβ families was responsible for the increased cytotoxicity observed, mAb specific for Vβ2 and Vβ6 were used to block tumor lysis. Anti-Vβ6 and anti-Vβ2 significantly blocked cytotoxicity against autologous tumor cells in those TIL populations expressing increased levels of these Vβ families. These data suggest that a selective repertoire of TCR Vβ genes is used to recognize the Ag-HLA class I complexes on the surface of ovarian tumor cells, and specifically Vβ2 and Vβ6 appear to mediate antitumor activity. These findings may aid in the development of a more specific immunotherapy in ovarian cancer.",
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