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Tumor-reactive T-Cells Accumulate in Lung Cancer Tissues but Fail to Respond Due to Tumor Cell-derived Factor¹

Departments of Virology [I. Y., G. K.], Immunology [M. M., K. N.], Medical Institute of Bioregulation, and Department of Surgery II, Faculty of Medicine, [T. I., K. S.], Kyushu University Fukuoka 812; and Department of Chest Surgery, National Kyushu Cancer Center, Fukuoka 815 [T. Y.], Japan

The purpose of this study was to elucidate a possible immune response to tumor cells mediated by tumor-infiltrating lymphocytes (TIL) in lung cancer. In flow cytometry, the majority of T-cells of TIL were CD45RA^–, CD45RO⁺, and CDw29^high, and expressed HLA-DR. The expression of interleukin 2 receptor ß chain increased in both CD4⁺ and CD8⁺ TIL compared with both types of T-cells in peripheral blood. These results indicate that the major population of TIL is activated memory T-cells. The TIL preparation, which was usually contaminated with 5 to 10% tumor cells, did not exhibit any response in autologous mixed lymphocyte-tumor culture even in the presence of interleukin 2 (IL-2) in all five cases tested. Although purified T-cells from TIL showed the positive response in only 1 of 10 cases tested without addition of IL-2, it occurred in 7 of 10 cases in the addition of a low concentration of IL-2. The IL-2-dependent response to irradiated autologous tumor cells was suppressed when nonirradiated autologous tumor cells were added to the culture. Culture supernatants of four lung cancer cell lines and freshly prepared lung cancer cells obtained from 6 cases exhibited suppressive activity against anti-CD3 antibody-induced mitogenesis of peripheral blood mononuclear cells from healthy donors. We suggest that, taken together, (a) the major population of TIL in lung cancer are activated memory T-cells, and they include tumor-reactive ones, and that (b) the function of the TIL is impaired by unavailability of IL-2 and/or by suppression due to lung cancer cell-derived factor(s).

¹ Supported in part by Grant 02557049 from Ministry of Education, Science and Culture, and a Grant-in-Aid for Cancer Research from Ministry of Health and Welfare, Japan.

² To whom requests for reprints should be addressed, at Department of Virology, Medical Institute of Bioregulation, Kyushu University 69, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812, Japan.

Received 7/12/91. Accepted 11/20/91.

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