T-cell recognition of ovarian cancer

Background. The existence of a tumor-specific T-cell immune response to human malignant melanoma has been well documented. In contrast, the existence of tumor-specific cytotoxic T lymphocyte to ovarian cancer remains controversial despite the abundant lymphocytic infiltrates in the malignant ascites and solid tumor of these patients. Methods. Tumor-associated lymphocytes (TAL) from the malignant ascites and tumor-infiltrating lymphocytes (TIL) from the solid tumors were isolated from six untreated patients with ovarian cancer. TAL and TIL were grown with initial anti- cluster of differentiation of T cells (CD3), low-dose interleukin-2, and tumor stimulation. T-cell lines were analyzed in functional studies. Results. At 5 weeks, TAL and TIL from five of six patients were >50% CD8⁺, and one of six was >70% CD4⁺. In all five pairs of CD8 positive cultures, both TAL and TIL exhibited high levels of tumor-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 TIL lysed autologous ascilic tumor equally well; however, TAL-mediated tumoricidal activity against autologous solid tumor was consistently and significantly poorer than TIL-mediated killing. Conclusions. Tumor-specific cytotoxic T lymphocytes can be expanded from both TAL and TIL. However, TAL do not kill solid tumor as efficiently as TIL. This suggests the requirement of TIL, or a combination of TIL and TAL, for effective immunotherapy.