小柯机器人

德国马格德堡大学Thomas Tüting等研究人员合作发现，CD4⁺T细胞诱导的炎症细胞死亡控制免疫侵袭性肿瘤。2023年6月14日，《自然》杂志在线发表了这项成果。

研究人员描述了一种机制，即少量的CD4⁺T细胞足以根除逃避CD8⁺T细胞直接靶向的MHC缺陷肿瘤。CD4⁺效应T细胞优先聚集在肿瘤浸润边缘，进而与MHC-II⁺CD11c⁺抗原呈递细胞相互作用。研究人员表明，1型T辅助细胞引导的CD4⁺T细胞和先天性免疫刺激将肿瘤相关的骨髓细胞网络重新编程为干扰素激活的抗原呈递和iNOS表达的杀伤性效应器表型。CD4⁺T细胞和杀伤性骨髓细胞共同协调了远程炎症细胞死亡的诱导，间接根除了对干扰素不敏感和MHC缺陷的肿瘤。这些结果证明了在临床上利用CD4⁺T细胞和先天性免疫刺激物的这种能力，从而补充CD8⁺T细胞和自然杀伤细胞的直接细胞溶解活性，推进癌症免疫治疗。

据介绍，大多数临床应用的癌症免疫疗法依赖于CD8⁺细胞溶解性T细胞直接识别和杀死肿瘤细胞的能力。这些策略受限于主要组织相容性复合体（MHC）缺陷的肿瘤细胞的出现和免疫抑制性肿瘤微环境的形成。CD4⁺效应细胞不依赖于CD8⁺T细胞为抗肿瘤免疫做出贡献的能力越来越被认可，但释放其全部潜力的策略仍有待确定。

附：英文原文

Title: CD4+ T cell-induced inflammatory cell death controls immune-evasive tumours

Author: Kruse, Bastian, Buzzai, Anthony C., Shridhar, Naveen, Braun, Andreas D., Gellert, Susan, Knauth, Kristin, Pozniak, Joanna, Peters, Johannes, Dittmann, Paulina, Mengoni, Miriam, van der Sluis, Tetje Cornelia, Hhn, Simon, Antoranz, Asier, Krone, Anna, Fu, Yan, Yu, Di, Essand, Magnus, Geffers, Robert, Mougiakakos, Dimitrios, Kahlfu, Sascha, Kashkar, Hamid, Gaffal, Evelyn, Bosisio, Francesca M., Bechter, Oliver, Rambow, Florian, Marine, Jean-Christophe, Kastenmller, Wolfgang, Mller, Andreas J., Tting, Thomas

Issue&Volume: 2023-06-14

Abstract: Most clinically applied cancer immunotherapies rely on the ability of CD8+ cytolytic T cells to directly recognize and kill tumour cells1,2,3. These strategies are limited by the emergence of major histocompatibility complex (MHC)-deficient tumour cells and the formation of an immunosuppressive tumour microenvironment4,5,6. The ability of CD4+ effector cells to contribute to antitumour immunity independently of CD8+ T cells is increasingly recognized, but strategies to unleash their full potential remain to be identified7,8,9,10. Here, we describe a mechanism whereby a small number of CD4+ T cells is sufficient to eradicate MHC-deficient tumours that escape direct CD8+ T cell targeting. The CD4+ effector T cells preferentially cluster at tumour invasive margins where they interact with MHC-II+CD11c+ antigen-presenting cells. We show that T helper type 1 cell-directed CD4+ T cells and innate immune stimulation reprogramme the tumour-associated myeloid cell network towards interferon-activated antigen-presenting and iNOS-expressing tumouricidal effector phenotypes. Together, CD4+ T cells and tumouricidal myeloid cells orchestrate the induction of remote inflammatory cell death that indirectly eradicates interferon-unresponsive and MHC-deficient tumours. These results warrant the clinical exploitation of this ability of CD4+ T cells and innate immune stimulators in a strategy to complement the direct cytolytic activity of CD8+ T cells and natural killer cells and advance cancer immunotherapies.

DOI: 10.1038/s41586-023-06199-x

Source: https://www.nature.com/articles/s41586-023-06199-x

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