T-CELL RECOGNITION OF OVARIAN-CANCER

Background. The existence of a tumor-specific T-cell immune response t o human malignant melanoma has been well documented In contrast, the e xistence of tumor-specific cytotoxic T lymphocyte to ovarian cancer re mains controversial despite the abundant lymphocytic infiltrates in th e malignant ascites and solid tumor of these patients. Methods. Tumor- associated lymphocytes (TAL) from the malignant ascites and tumor-infi ltrating lymphocytes (TIL) from the solid tumors were isolated from si x untreated patients with ovarian cancer. TAL and TIL were grown with initial anti-cluster of differentiation of T cells (CD3), low-dose int erleukin-2, and tumor stimulation. T-cell lines were analyzed in funct ional studies. Results. At 5 weeks, TAL and TIL from five of six patie nts were >50% CD8+, and one of six was > 70% CD4+. In all five pairs o f CD8 positive cultures, both TAL and TIL exhibited high levels of tum or-specific cytotoxicity for ascitic and solid tumor, respectively. T- cell recognition of tumor was mediated through the T-cell receptor-CD3 complex and was human leukocyte antigen class I restricted TAL and TI L lysed autologous ascitic tumor equally well; however, TAL-mediated t umoricidal activity against autologous solid tumor was consistently an d significantly poorer than TIL-mediated killing. Conclusions. Tumor-s pecific cytotoxic T lymphocytes can be expanded from both TAL and TIL. However, TAL do not kill solid tumor as efficiently as TIL. This sugg ests the requirement of TIL, or a combination of TIL and TAL, for effe ctive immunotherapy.