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TGF-β 抑制癌症的 2 型免疫。

TGF-β suppresses type 2 immunity to cancer.

机构信息

Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Immunogenomics and Precision Oncology Platform (IPOP), Memorial Sloan Kettering Cancer Center, New York, NY, USA.

出版信息

Nature. 2020 Nov;587(7832):115-120. doi: 10.1038/s41586-020-2836-1. Epub 2020 Oct 21.

DOI:10.1038/s41586-020-2836-1
PMID:33087928
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8347705/
Abstract

The immune system uses two distinct defence strategies against infections: microbe-directed pathogen destruction characterized by type 1 immunity, and host-directed pathogen containment exemplified by type 2 immunity in induction of tissue repair. Similar to infectious diseases, cancer progresses with self-propagating cancer cells inflicting host-tissue damage. The immunological mechanisms of cancer cell destruction are well defined, but whether immune-mediated cancer cell containment can be induced remains poorly understood. Here we show that depletion of transforming growth factor-β receptor 2 (TGFBR2) in CD4 T cells, but not CD8 T cells, halts cancer progression as a result of tissue healing and remodelling of the blood vasculature, causing cancer cell hypoxia and death in distant avascular regions. Notably, the host-directed protective response is dependent on the T helper 2 cytokine interleukin-4 (IL-4), but not the T helper 1 cytokine interferon-γ (IFN-γ). Thus, type 2 immunity can be mobilized as an effective tissue-level defence mechanism against cancer.

摘要

免疫系统利用两种截然不同的防御策略来对抗感染

以 1 型免疫为特征的针对微生物的病原体破坏，以及以 2 型免疫为代表的诱导组织修复的针对宿主的病原体控制。与传染病类似，癌症的进展伴随着自我传播的癌细胞对宿主组织造成损伤。癌症细胞破坏的免疫机制已经得到很好的定义，但免疫介导的癌症细胞控制是否可以被诱导仍然知之甚少。在这里，我们表明，CD4 T 细胞中转化生长因子-β受体 2 (TGFBR2) 的耗竭会导致组织愈合和血管重塑，从而阻止癌症的进展，导致远离无血管区域的癌症细胞缺氧和死亡。值得注意的是，这种宿主定向的保护反应依赖于辅助性 T 细胞 2 型细胞因子白细胞介素-4 (IL-4)，而不是辅助性 T 细胞 1 型细胞因子干扰素-γ (IFN-γ)。因此，2 型免疫可以被动员为一种针对癌症的有效的组织水平防御机制。

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