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ILC3的失调促进结肠癌的进展和免疫疗法的抗性
作者:小柯机器人 发布时间:2021/8/22 10:34:40

美国康奈尔大学Gregory F. Sonnenberg课题组发现,ILC3的失调促进结肠癌的进展和免疫疗法的抗性。相关论文于2021年8月17日在线发表于国际学术期刊《细胞》。

研究人员发现结直肠癌(CRC)表现为第3组先天性淋巴细胞(ILC3)的改变,其特点是频率降低,可塑性增加,并与T细胞不平衡。研究人员评估了这些变化对小鼠的影响,并确定ILC3和T细胞之间通过II类主要组织相容性复合体(MHCII)的对话对于支持微生物群的定植是必要的,这些微生物群随后在肠道和肿瘤微环境中诱导了1型免疫力。因此,缺乏ILC3特异性MHCII的小鼠会发展成侵袭性CRC,并对抗PD-1免疫疗法产生抗性。

最后,患有肠道ILC3失调的人类携带的微生物群在转移到小鼠身上时不能诱导1型免疫和免疫疗法的反应性。总的来说,这些数据确定了ILC3在癌症中的保护作用,并表明它们在CRC中的固有干扰会导致适应性免疫功能失调、肿瘤进展和免疫疗法的抗性。

据介绍,ILC3调节免疫和炎症,但它们在癌症中的作用仍然难以确定。

附:英文原文

Title: Dysregulation of ILC3s unleashes progression and immunotherapy resistance in colon cancer

Author: Jeremy Goc, Mengze Lv, Nicholas J. Bessman, Anne-Laure Flamar, Sheena Sahota, Hiroaki Suzuki, Fei Teng, Gregory G. Putzel, Gerard Eberl, David R. Withers, Janelle C. Arthur, Manish A. Shah, Gregory F. Sonnenberg

Issue&Volume: 2021-08-17

Abstract: Group 3 innate lymphoid cells (ILC3s) regulate immunity and inflammation, yet theirrole in cancer remains elusive. Here, we identify that colorectal cancer (CRC) manifestswith altered ILC3s that are characterized by reduced frequencies, increased plasticity,and an imbalance with T cells. We evaluated the consequences of these changes in miceand determined that a dialog between ILC3s and T cells via major histocompatibilitycomplex class II (MHCII) is necessary to support colonization with microbiota thatsubsequently induce type-1 immunity in the intestine and tumor microenvironment. Asa result, mice lacking ILC3-specific MHCII develop invasive CRC and resistance toanti-PD-1 immunotherapy. Finally, humans with dysregulated intestinal ILC3s harbormicrobiota that fail to induce type-1 immunity and immunotherapy responsiveness whentransferred to mice. Collectively, these data define a protective role for ILC3s incancer and indicate that their inherent disruption in CRC drives dysfunctional adaptiveimmunity, tumor progression, and immunotherapy resistance.

DOI: 10.1016/j.cell.2021.07.029

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00888-6

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/