A Critical Requirement of Interferon {gamma}-mediated Angiostasis for Tumor Rejection by CD8+ T Cells

Immunology

A Critical Requirement of Interferon ${gamma}$ -mediated Angiostasis for Tumor Rejection by CD8⁺ T Cells¹

Zhihai Qin², Johannes Schwartzkopff, Felicia Pradera, Thomas Kammert $oe$ ns, Barbara Seliger, Hanspeter Pircher and Thomas Blankenstein

Institute of Immunology, University Clinic Benjamin-Franklin, Free University of Berlin, 12200 Berlin [Z. Q., T. B.]; Institute of Medical Microbiology and Hygiene, Department of Immunology, University of Freiburg, 79104 Freiburg [J. S., H. P.]; Max-Delbrück-Center for Molecular Medicine, 13092 Berlin [F. P., T. K., T. B.]; and Third Department of Internal Medicine, Johannes Gutenberg-University, 55131 Mainz [B. S.], Germany

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

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