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ILC2通过激活组织特异性肿瘤免疫放大PD-1抑制
2020-02-21 10:33
来源：小柯机器人

2型先天淋巴样细胞（ILC2）通过激活组织特异性肿瘤免疫放大PD-1抑制，这一成果由美国纪念斯隆-凯特琳癌症中心Vinod P. Balachandran、Taha Merghoub等研究人员合作完成。相关论文于2020年2月19日在线发表在《自然》杂志上。

研究人员发现，ILC2浸润胰腺导管腺癌（PDAC）从而激活组织特异性肿瘤免疫。白介素33（IL33）激活小鼠原位胰腺肿瘤中的肿瘤ILC2（TILC2）和CD8+T细胞，但不激活小鼠异位皮肤肿瘤，从而限制胰腺特异性肿瘤的生长。
 
静止和激活的TILC2表达抑制性检查点受体PD-1。抗体介导的PD-1阻断可减轻ILC2细胞固有的PD-1抑制，从而扩增TILC2，增强抗肿瘤免疫并增强肿瘤控制，因此活化的TILC2被确定为抗PD-1免疫疗法的靶标。
 
最后，PD-1+TILC2和PD-1+T细胞都存在于大多数人类PDAC中。这些结果确定ILC2为PDAC免疫疗法的抗癌免疫细胞。
 
具体而言，ILC2作为癌症免疫的组织特异性增强因素出现，可增强抗PD-1免疫疗法的功效。由于ILC2和T细胞共存于人类癌症中，并具有刺激性和抑制性途径，因此共同靶向抗癌ILC2和T细胞的免疫治疗策略可能会广泛应用。
 
据悉，2型先天淋巴样细胞（ILC2）调节哺乳动物组织中的炎症和免疫。尽管在这些组织的癌症中发现了ILC2，但它们在癌症免疫和免疫治疗中的作用尚不清楚。
 
附：英文原文

Title: ILC2s amplify PD-1 blockade by activating tissue-specific cancer immunity

Author: John Alec Moral, Joanne Leung, Luis A. Rojas, Jennifer Ruan, Julia Zhao, Zachary Sethna, Anita Ramnarain, Billel Gasmi, Murali Gururajan, David Redmond, Gokce Askan, Umesh Bhanot, Ela Elyada, Youngkyu Park, David A. Tuveson, Mithat Gnen, Steven D. Leach, Jedd D. Wolchok, Ronald P. DeMatteo, Taha Merghoub, Vinod P. Balachandran

Issue&Volume: 2020-02-19

Abstract: Group 2 innate lymphoid cells (ILC2s) regulate inflammation and immunity in mammalian tissues1,2. Although ILC2s are found in cancers of these tissues3, their roles in cancer immunity and immunotherapy are unclear. Here we show that ILC2s infiltrate pancreatic ductal adenocarcinomas (PDACs) to activate tissue-specific tumour immunity. Interleukin-33 (IL33) activates tumour ILC2s (TILC2s) and CD8+ T cells in orthotopic pancreatic tumours but not heterotopic skin tumours in mice to restrict pancreas-specific tumour growth. Resting and activated TILC2s express the inhibitory checkpoint receptor PD-1. Antibody-mediated PD-1 blockade relieves ILC2 cell-intrinsic PD-1 inhibition to expand TILC2s, augment anti-tumour immunity, and enhance tumour control, identifying activated TILC2s as targets of anti-PD-1 immunotherapy. Finally, both PD-1+ TILC2s and PD-1+ T cells are present in most human PDACs. Our results identify ILC2s as anti-cancer immune cells for PDAC immunotherapy. More broadly, ILC2s emerge as tissue-specific enhancers of cancer immunity that amplify the efficacy of anti-PD-1 immunotherapy. As ILC2s and T cells co-exist in human cancers and share stimulatory and inhibitory pathways, immunotherapeutic strategies to collectively target anti-cancer ILC2s and T cells may be broadly applicable.

DOI: 10.1038/s41586-020-2015-4

Source: https://www.nature.com/articles/s41586-020-2015-4

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html


本期文章：《自然》：Online/在线发表

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