γ干扰素介导的血管生成抑制对于CD8 + T细胞排斥肿瘤的关键要求。

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

作者信息

Qin Zhihai, Schwartzkopff Johannes, Pradera Felicia, Kammertoens Thomas, Seliger Barbara, Pircher Hanspeter, Blankenstein Thomas

机构信息

Institute of Immunology, University Clinic Benjamin-Franklin, Free University of Berlin, 12200 Berlin, Germany.

出版信息

Cancer Res. 2003 Jul 15;63(14):4095-100.

PMID:12874012

Abstract

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.

摘要

人们认为，CD8(+) T细胞效应器介导的肿瘤排斥主要是通过直接杀伤来实现的。我们发现，CD8(+) T细胞对不同肿瘤（纤维肉瘤、ras转化的成纤维细胞、结肠癌和浆细胞瘤）的排斥总是先于对肿瘤诱导的血管生成的抑制。在穿孔素缺陷小鼠中观察到血管生成抑制和肿瘤排斥，但在IFN-γ缺陷小鼠中未观察到。此外，与来自IFN-γ基因缺陷小鼠的肿瘤特异性CD8(+) T细胞相比，来自IFN-γ功能正常小鼠的肿瘤特异性CD8(+) T细胞的过继转移抑制了肺转移瘤的血管生成。结合我们之前的研究结果，我们得出结论，IFN-γ依赖性抗血管生成是CD4(+)和CD8(+) T细胞效应器介导肿瘤排斥所涉及的一种普遍机制。