Dysregulation of ILC3s unleashes progression and immunotherapy resistance in colon cancer.
Dysregulation of ILC3s unleashes progression and immunotherapy resistance in colon cancer.
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DOI：
10.1016/j.cell.2021.07.029
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发表时间：
2021-09-16
期刊：
影响因子：
64.5
通讯作者：
Sonnenberg GF
中科院分区：
文献类型：
--
作者：
Goc J;Lv M;Bessman NJ;Flamar AL;Sahota S;Suzuki H;Teng F;Putzel GG;JRI Live Cell Bank;Eberl G;Withers DR;Arthur JC;Shah MA;Sonnenberg GF
第三组先天淋巴样细胞(ILC3)调节免疫和炎症，但它们在癌症中的作用仍不清楚。在这里，我们确认结直肠癌(CRC)表现为ILC3的改变，其特征是频率降低，可塑性增加，与T细胞的失衡。我们评估了这些变化在小鼠身上的后果，并确定通过主要组织相容性复合体II类(MHCII)在ILC3和T细胞之间进行对话对于支持微生物群的定植是必要的，微生物群随后在肠道和肿瘤微环境中诱导类型1免疫。因此，缺乏ILC3特异性MHCII的小鼠会发展为侵袭性CRC并对抗PD-1免疫治疗产生抵抗力。最后，肠道ILC3s调节失调的人体内有微生物区系，当转移到小鼠身上时，这些微生物群无法诱导1型免疫和免疫治疗反应。总而言之，这些数据定义了ILC3在癌症中的保护作用，并表明它们在CRC中的固有破坏导致了功能失调的适应性免疫、肿瘤进展和免疫治疗抵抗。在患有结直肠癌的人的肿瘤微环境中，ILC3会发生变化，类似于在发炎的肠道中发现的那些。在小鼠中，ILC3s调节适应性免疫，塑造微生物区系组成，防止肿瘤进展和结直肠癌免疫治疗抵抗。
Group 3 innate lymphoid cells (ILC3s) regulate immunity and inflammation, yet their role in cancer remains elusive. Here, we identify that colorectal cancer (CRC) manifests with altered ILC3s that are characterized by reduced frequencies, increased plasticity, and an imbalance with T cells. We evaluated the consequences of these changes in mice and determined that a dialogue between ILC3s and T cells via major histocompatibility complex class II (MHCII) is necessary to support colonization with microbiota that subsequently induce type-1 immunity in the intestine and tumor microenvironment. As a result, mice lacking ILC3-specific MHCII develop invasive CRC and resistance to anti-PD-1 immunotherapy. Finally, humans with dysregulated intestinal ILC3s harbor microbiota that fail to induce type-1 immunity and immunotherapy responsiveness when transferred to mice. Collectively, these data define a protective role for ILC3s in cancer and indicate that their inherent disruption in CRC drives dysfunctional adaptive immunity, tumor progression and immunotherapy resistance. ILC3s are altered in the tumor microenvironment of humans with colorectal cancer, resembling those found in the inflamed intestine. In mice, ILC3s regulate adaptive immunity, shape the microbiota composition and protect from tumor progression as well as colorectal cancer immunotherapy resistance.
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影响因子：
32.4
作者：
Colonna M
通讯作者：
Colonna M
DOI：
10.1126/science.aan4526
发表时间：
2017-10-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Atarashi K;Suda W;Luo C;Kawaguchi T;Motoo I;Narushima S;Kiguchi Y;Yasuma K;Watanabe E;Tanoue T;Thaiss CA;Sato M;Toyooka K;Said HS;Yamagami H;Rice SA;Gevers D;Johnson RC;Segre JA;Chen K;Kolls JK;Elinav E;Morita H;Xavier RJ;Hattori M;Honda K
通讯作者：
Honda K
影响因子：
10.5
作者：
Brennan CA;Garrett WS
通讯作者：
Garrett WS
影响因子：
32.4
作者：
Bernink, Jochem H.;Krabbendam, Lisette;Spits, Hergen
通讯作者：
Spits, Hergen
影响因子：
8
作者：
Chan, I. H.;Jain, R.;LaFace, D.
通讯作者：
LaFace, D.