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研究揭示ILC2促进癌症肺部转移的机制

本期文章:《自然—免疫学》:Online/在线发表

英国剑桥大学Timotheus Y. F. Halim研究团队的最新研究,揭示了在肺部ILC2诱导的先天免疫检查点机制拮抗NK细胞的抗转移功能。相关论文发表在2020年8月3日出版的《自然-免疫学》杂志上。

研究人员发现,肺部驻留2型先天淋巴样细胞(ILC2s)的激活有效抑制了自然杀伤(NK)细胞介导的先天抗肿瘤免疫,这导致肺转移和死亡率增加。使用多种肺转移模型,研究人员发现肺部白介素(IL)-33依赖的ILC2激活主要参与了肿瘤负荷。ILC2诱导的2型先天性炎症伴随着干扰素-γ的产生和肺部NK细胞细胞毒性功能的局部抑制。

ILC2依赖的NK细胞抑制是通过一种固有的调节机制实现的,该机制依赖于IL-5诱导的肺嗜酸性粒细胞增多,最终妨碍了NK细胞的代谢适应性。靶向IL-33或IL-5的治疗可逆转NK细胞抑制并减轻肺部癌症负荷。因此,该研究揭示了IL-33和ILC2s通过抑制1型先天性免疫促进肿瘤转移的机制。

研究人员表示,转移是造成癌症死亡的主要原因,而肺是常见的受累器官。

附:英文原文

Title: ILC2-driven innate immune checkpoint mechanism antagonizes NK cell antimetastatic function in the lung

Author: Martijn J. Schuijs, Shaun Png, Arianne C. Richard, Anastasia Tsyben, Gregory Hamm, Julie Stockis, Celine Garcia, Silvain Pinaud, Ashley Nicholls, Xavier Romero Ros, Jing Su, Matthew D. Eldridge, Angela Riedel, Eva M. Serrao, Hans-Reimer Rodewald, Matthias Mack, Jacqueline D. Shields, E. Suzanne Cohen, Andrew N. J. McKenzie, Richard J. A. Goodwin, Kevin M. Brindle, John C. Marioni, Timotheus Y. F. Halim

Issue&Volume: 2020-08-03

Abstract: Metastasis constitutes the primary cause of cancer-related deaths, with the lung being a commonly affected organ. We found that activation of lung-resident group 2 innate lymphoid cells (ILC2s) orchestrated suppression of natural killer (NK) cell-mediated innate antitumor immunity, leading to increased lung metastases and mortality. Using multiple models of lung metastasis, we show that interleukin (IL)-33-dependent ILC2 activation in the lung is involved centrally in promoting tumor burden. ILC2-driven innate type 2 inflammation is accompanied by profound local suppression of interferon-γ production and cytotoxic function of lung NK cells. ILC2-dependent suppression of NK cells is elaborated via an innate regulatory mechanism, which is reliant on IL-5-induced lung eosinophilia, ultimately limiting the metabolic fitness of NK cells. Therapeutic targeting of IL-33 or IL-5 reversed NK cell suppression and alleviated cancer burden. Thus, we reveal an important function of IL-33 and ILC2s in promoting tumor metastasis via their capacity to suppress innate type 1 immunity. Pathological group 2 innate lymphoid cells (ILC2s) have mainly been implicated in allergy. Halim and colleagues demonstrate that ILC2s orchestrate a prometastatic pathway via the recruitment of eosinophils that suppress NK cell function.

DOI: 10.1038/s41590-020-0745-y

Source: https://www.nature.com/articles/s41590-020-0745-y

期刊信息

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex

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