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.
Qin
Zhihai
Z
Institute of Immunology, University Clinic Benjamin-Franklin, Free University of Berlin, 12200 Berlin, Germany. zhihai@ukbf.fu-berlin.de
Schwartzkopff
Johannes
J
Pradera
Felicia
F
Kammertoens
Thomas
T
Seliger
Barbara
B
Pircher
Hanspeter
H
Blankenstein
Thomas
T
D016475:3T3 Cells; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005354:Fibrosarcoma / Q000098:blood supply / Q000276:immunology / Q000628:therapy; D007114:Immunization; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology*; D008546:Melanoma, Experimental / Q000098:blood supply / Q000276:immunology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000276:immunology* / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000276:immunology* / Q000517:prevention & control
D007371:Interferon-gamma