研究揭示cCD1引发抗肿瘤免疫机制-小柯机器人-科学网

研究揭示cCD1引发抗肿瘤免疫机制

2020-08-14 17:50

美国华盛顿大学医学院Kenneth M. Murphy团队的最新工作揭示了cCD1引发抗肿瘤免疫的机制。这一研究成果于2020年8月12日在线发表在《自然》上。

研究人员表示，常规1型树突状细胞（cDC1）被认为执行抗原交叉呈递，这是活化CD8⁺T细胞所必需的，而cDC2专用于活化CD4⁺T细胞。CD4⁺T细胞也被认为可以通过多种机制帮助CD8⁺T细胞反应，包括CD4⁺T细胞“许可” cDC1进行CD8⁺T细胞活化的过程。但是，该模型尚未在体内或在依赖帮助的肿瘤排斥情况下直接测试。

研究人员生成了Xcr1^Cre小鼠品系，用于评估在需要CD4⁺和CD8⁺T细胞模型中介导肿瘤排斥的细胞相互作用。如预期的那样，肿瘤排斥需要cDC1，而CD8⁺T细胞活化则需要cDC1表达主要组织相容性I类分子。出乎意料的是，针对肿瘤来源抗原的CD4⁺T细胞的早期活化也需要cDC1，这不仅是因为它们将抗原转运到淋巴结以进行cDC2的处理，因为在cDC1中选择性删除主要组织相容性II类分子也阻止了早期的CD4⁺T细胞活化。

此外，cDC1中主要组织相容性II类或CD40的缺失会损害肿瘤排斥，这与cDC1许可中相关CD4⁺T细胞相互作用和CD40信号传导的作用一致。最后，cDC1中的CD40信号传导不仅对于CD8⁺T细胞活化至关重要，而且对于初始CD4⁺T细胞激活也至关重要。因此，在肿瘤衍生抗原的背景下，cDC1充当了一个自主平台，能够对CD4⁺和CD8⁺T细胞进行抗原加工和活化，并能够直接编排最佳抗肿瘤免疫所需的互作。

附：英文原文

Title: cDC1 prime and are licensed by CD4 + T cells to induce anti-tumour immunity

Author: Stephen T. Ferris, Vivek Durai, Renee Wu, Derek J. Theisen, Jeffrey P. Ward, Michael D. Bern, Jesse T. Davidson, Prachi Bagadia, Tiantian Liu, Carlos G. Briseo, Lijin Li, William E. Gillanders, Gregory F. Wu, Wayne M. Yokoyama, Theresa L. Murphy, Robert D. Schreiber, Kenneth M. Murphy

Issue&Volume: 2020-08-12

Abstract: Conventional type 1 dendritic cells (cDC1)1 are thought to perform antigen cross-presentation, which is required to prime CD8+ T cells2,3, whereas cDC2 are specialized for priming CD4+ T cells4,5. CD4+ T cells are also considered to help CD8+ T cell responses through a variety of mechanisms6,7,8,9,10,11, including a process whereby CD4+ T cells ‘license’ cDC1 for CD8+ T cell priming12. However, this model has not been directly tested in vivo or in the setting of help-dependent tumour rejection. Here we generated an Xcr1Cre mouse strain to evaluate the cellular interactions that mediate tumour rejection in a model requiring CD4+ and CD8+ T cells. As expected, tumour rejection required cDC1 and CD8+ T cell priming required the expression of major histocompatibility class I molecules by cDC1. Unexpectedly, early priming of CD4+ T cells against tumour-derived antigens also required cDC1, and this was not simply because they transport antigens to lymph nodes for processing by cDC2, as selective deletion of major histocompatibility class II molecules in cDC1 also prevented early CD4+ T cell priming. Furthermore, deletion of either major histocompatibility class II or CD40 in cDC1 impaired tumour rejection, consistent with a role for cognate CD4+ T cell interactions and CD40 signalling in cDC1 licensing. Finally, CD40 signalling in cDC1 was critical not only for CD8+ T cell priming, but also for initial CD4+ T cell activation. Thus, in the setting of tumour-derived antigens, cDC1 function as an autonomous platform capable of antigen processing and priming for both CD4+ and CD8+ T cells and of the direct orchestration of their cross-talk that is required for optimal anti-tumour immunity.

DOI: 10.1038/s41586-020-2611-3

Source: https://www.nature.com/articles/s41586-020-2611-3

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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