Tumor-infiltrating lymphocytes from human ovarian cancer patients recognize autologous tumor in an MHC class II-restricted fashion

PURPOSE: To search for tumor-specific in vitro reactivity by lymphocytes derived from patients with ovarian carcinoma. METHODS: Tumor-infiltrating lymphocytes (TIL) were derived from primary or metastatic solid tumors and tumor-associated lymphocytes (TAL) were derived from ascites from 13 patients with ovarian cancer. TIL or TAL were cultured for approximately 30 to 60 days and studied for phenotype, cytotoxicity, and cytokine secretion in response to autologous tumor stimulation. RESULTS: Twenty-nine bulk TIL or TAL cultures were successfully established from 10 patients using various culture conditions. Thirteen cultures were predominantly CD4+ and 16 were mainly CD8+. In contrast to reports by others, none of the cultures tested were specifically lytic for autologous tumor. Five predominantly CD4+ bulk TIL (from four patients) preferentially secreted tumor necrosis factor-α and granulocyte macrophage-colony stimulating factor when stimulated with autologous tumor and not when stimulated by autologous Epstein Barr virus-B cells, fibroblasts, peripheral blood mononuclear cells, or allogeneic HLA matched or mismatched stimulators. This cytokine secretion was found to be MHC class-II restricted in three patients because it was inhibited by the anti-MHC class-II antibody IVA12 and the HLA-DR specific antibody L243. CONCLUSION: We believe these data are the first to suggest that tumor reactive CD4+ lymphocytes exist in some ovarian cancer patients. This finding may be useful in the development of novel immunotherapies for these patients.