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Characterization of Human Autotumor-Reactive T-Cell Clones Obtained from Tumor-infiltrating Lymphocytes in Liver Metastasis of Gastric Carcinoma¹

Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213 [Y. S., E. W., S. I., R. B. H., T. L. W.], and Departments of Surgery [S. I.], Pathology [Y. S., E. W., R. B. H., T. L. W.], and Medicine [R.B.H.], University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261

Three autotumor-reactive T-cell clones have been established from tumor-infiltrating lymphocytes isolated from a metastatic lesion of human gastric carcinoma in the liver. The clones all were shown to be CD3⁺, CD8⁺, CD4^–, CD16^–, T-cell receptor /ß⁺, and T-cell receptor /^–, and they have retained both their autotumor reactivity and the same phenotype for over a year in culture. Each clone had a different rearrangement of the T-cell receptor chain genes as indicated by Southern blot analysis. Tested against a panel of 18 tumor cell targets, the clones preferentially lysed autologous tumor (AuTu) cells, but each clone also showed weak cytotoxicity against one allogeneic cholangiocarcinoma cell line. At the same time, each clone showed appreciable cytotoxicity against K562 targets. In blocking experiments, anti-CD3, anti-WT31, anti-CD8, or anti-HLA class I monoclonal antibodies blocked AuTu cytotoxicity but not cytotoxicity against K562. In contrast, allocytotoxicity against the cholangiocarcinoma was blocked only by anti-CD3 monoclonal antibody. All 10 subclones of one T-cell clone had high levels of AuTu cytotoxicity but variable levels of anti-K562 cytotoxic activity. Proliferation of the T-cell clones was significantly stimulated by the addition of irradiated autologous but not allogeneic tumor cells. Preincubation of cultured AuTu cells with tumor necrosis factor or -interferon (IFN-), but not with IFN-, increased their susceptibility to lysis by the T-cell clones; however, it increased resistance of AuTu to lysis by interleukin 2-activated natural killer cells. The expression of an adhesion molecule, intercellular adhesion molecule 1, on the surface of AuTu was also up-regulated by tumor necrosis factor or IFN-, but not by IFN-. All three cytokines up-regulated HLA-class-I antigens on AuTu. Pretreatment of K562 targets or allogeneic cholangiocarcinoma cells with the same cytokines increased their resistance to lysis by the T-cell clones. Overall, the results indicate that these T-cell clones show specificity for AuTu but also independently recognize a limited number of allogeneic tumor targets and lyse K562 targets. The mechanisms involved in the recognition by the T-cell clones of autologous, allogeneic, and K562 tumor targets appeared to be distinct.

¹ This work was supported in part by ACS Grant IM588 (T. L. W.) and National Cancer Institute Program Project 1PO1-CA-4744501.

² To whom requests for reprints should be addressed, at Pittsburgh Cancer Institute, W1041, Biomedical Science Tower, DeSoto at O'Hara Street, Pittsburgh, PA 15213.

Received 5/ 2/91. Accepted 9/10/91.

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