The Journal of Immunology, Vol 151, Issue 10 5472-5480, Copyright © 1993 by American Association of Immunologists

ARTICLES

T cell receptor V beta 2 and V beta 6 mediate tumor-specific cytotoxicity by tumor-infiltrating lymphocytes in ovarian cancer

GE Peoples, MP Davey, PS Goedegebuure, DD Schoof and TJ Eberlein
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.

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 beta-chain (V beta). To determine whether a restricted number of TCR V beta 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 V beta 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 V beta gene families were employed and amplified by polymerase chain reaction and then quantitated by HPLC. A heterogeneous pattern of V beta usage was seen in the fresh TIL; however, V beta 2, V beta 3, V beta 6, V beta 7, V beta 8, and V beta 13.1 were found in increased proportions in at least three of five patients. In the 7-wk tumor-specific TIL, V beta analysis showed an increased usage of V beta 2, V beta 3, V beta 6, and V beta 7 in more than three of five patients. No significant change in V beta representation was seen in control populations that were not stimulated with tumor. Looking at the percent change in V beta usage between fresh and 7-wk tumor-specific cultures, V beta 2 and V beta 6 were augmented significantly in at least three of five patients (108% and 61%, respectively). To verify that the increase in representation of these V beta families was responsible for the increased cytotoxicity observed, mAb specific for V beta 2 and V beta 6 were used to block tumor lysis. Anti-V beta 6 and anti-V beta 2 significantly blocked cytotoxicity against autologous tumor cells in those TIL populations expressing increased levels of these V beta families. These data suggest that a selective repertoire of TCR V beta genes is used to recognize the Ag-HLA class 1 complexes on the surface of ovarian tumor cells, and specifically V beta 2 and V beta 6 appear to mediate antitumor activity. These findings may aid in the development of a more specific immunotherapy in ovarian cancer.

This article has been cited by other articles:

				R. A. Kurt, J. A. Park, S. F. Schluter, J. J. Marchalonis, and E. T. Akporiaye TCR V{beta} usage and clonality of T cells isolated from progressing and rejected tumor sites before and after in vitro culture Int. Immunol., May 1, 2000; 12(5): 639 - 646. [Abstract] [Full Text] [PDF]

				H. Echchakir, I. Vergnon, G. Dorothee, D. Grunenwald, S. Chouaib, and F. Mami-Chouaib Evidence for in situ expansion of diverse antitumor-specific cytotoxic T lymphocyte clones in a human large cell carcinoma of the lung Int. Immunol., April 1, 2000; 12(4): 537 - 546. [Abstract] [Full Text] [PDF]

				M. Hishii, D. Andrews, L. A. Boyle, J. T. Wong, F. Pandolfi, P. J. van den Elsen, and J. T. Kurnick In vivo accumulation of the same anti-melanoma T cell clone in two different metastatic sites PNAS, February 18, 1997; 94(4): 1378 - 1383. [Abstract] [Full Text] [PDF]