A critical requirement of interferon gamma-mediated angiostasis for tumor rejection by CD8+ T cells.

It is thought that tumor rejection by CD8(+) T-cell effectors is primarily mediated by direct killing. We show that rejection of different tumors (fibrosarcoma, ras-transformed fibroblasts, colon carcinoma, and plasmacytoma) by CD8(+) T cells is always preceded by inhibition of tumor-induced angiogenesis. Angiostasis and tumor rejection were observed in perforin but not in IFN-gamma-deficient mice. Furthermore, adoptive transfer of tumor-specific CD8(+) T cells from IFN-gamma-competent mice inhibited angiogenesis of lung metastases in comparison to those from IFN-gamma gene-deficient mice. Taken together with our previous findings, we conclude that IFN-gamma-dependent antiangiogenesis is a general mechanism involved in tumor rejection by CD4(+) and CD8(+) T-cell effectors.