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[Fundamental and clinical aspects of adoptive immunotherapy with tumor-infiltrating lymphocytes]
1Dept. of Obstetrics and Gynecology, Niigata University, School of Medicine.
Fundamental analysis was conducted on the phenotype and function of autologous tumor-infiltrating lymphocytes (TIL) in terms of their role as effector cells in specific immunotherapy for malignant tumors. Their effects were further examined in a preliminary clinical study. Analysis of the phenotype of lymphocytes which infiltrate tumor tissue and proliferate in the presence of IL-2, by using cell-surface subset markers, revealed proliferation of two types of lymphocytes: CD8-positive cytotoxic/suppressor T-cells and CD4-positive helper/suppressor inducer T-cells. In vitro cytotoxicity tests on these lymphocytes for antitumor activity showed that only CD8-positive lymphocytes had a much stronger antitumor effect on autologous tumor cells than LAK cells. In contrast, they showed no antitumor effect on autologous normal cells or homologous tumor cells of the same histological type, indicating specificity of their antitumor activity. Furthermore, in vitro treatment of tumor cells with interferon was found to increase both expression of MHC class I antigens and sensitivity to TIL cytotoxicity. In vitro of the close relationship between induction of CD8-positive TIL and expression of HLA (A, B, C) antigens in tumor tissue, the above findings suggest that the presence or absence of expression of MHC class I antigens plays an important role in the efficacy of adoptive immunotherapy with TIL. Significant antitumor activity was observed in patients given CD8-positive cells in a preliminary clinical study, the same as in in vitro assay. No patient showed serious side effects such as the pulmonary edema or body fluid retention observed in LAK therapy. Specific immunotherapy using TIL seems to be a promising modality in multidisciplinary treatment of cancer. Further developments from research on this subject are expected.
Fundamental analysis was conducted on the phenotype and function of autologous tumor-infiltrating lymphocytes (TIL) in terms of their role as effector cells in specific immunotherapy for malignant tumors. Their effects were further examined in a preliminary clinical study. Analysis of the phenotype of lymphocytes which infiltrate tumor tissue and proliferate in the presence of IL-2, by using cell-surface subset markers, revealed proliferation of two types of lymphocytes: CD8-positive cytotoxic/suppressor T-cells and CD4-positive helper/suppressor inducer T-cells. In vitro cytotoxicity tests on these lymphocytes for antitumor activity showed that only CD8-positive lymphocytes had a much stronger antitumor effect on autologous tumor cells than LAK cells. In contrast, they showed no antitumor effect on autologous normal cells or homologous tumor cells of the same histological type, indicating specificity of their antitumor activity. Furthermore, in vitro treatment of tumor cells with interferon was found to increase both expression of MHC class I antigens and sensitivity to TIL cytotoxicity. In vitro of the close relationship between induction of CD8-positive TIL and expression of HLA (A, B, C) antigens in tumor tissue, the above findings suggest that the presence or absence of expression of MHC class I antigens plays an important role in the efficacy of adoptive immunotherapy with TIL. Significant antitumor activity was observed in patients given CD8-positive cells in a preliminary clinical study, the same as in in vitro assay. No patient showed serious side effects such as the pulmonary edema or body fluid retention observed in LAK therapy. Specific immunotherapy using TIL seems to be a promising modality in multidisciplinary treatment of cancer. Further developments from research on this subject are expected.