2. Academic Validation
  3. Transdifferentiation of tumor infiltrating innate lymphoid cells during progression of colorectal cancer

Transdifferentiation of tumor infiltrating innate lymphoid cells during progression of colorectal cancer

  • Cell Res. 2020 Jul;30(7):610-622. doi: 10.1038/s41422-020-0312-y.
Shuo Wang  # 1 2 3,  Yuan Qu  # 4 5,  Pengyan Xia  # 4 6,  Yi Chen  # 7,  Xiaoxiao Zhu 8,  Jing Zhang 9,  Guan Wang 7,  Yong Tian 10,  Jianming Ying 11,  Zusen Fan 4 5
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Infection and Immunity, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, China. wangshuo@im.ac.cn.
  • 2 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, 100101, Beijing, China. wangshuo@im.ac.cn.
  • 3 Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, Hubei, China. wangshuo@im.ac.cn.
  • 4 CAS Key Laboratory of Infection and Immunity, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, China.
  • 5 University of Chinese Academy of Sciences, 100049, Beijing, China.
  • 6 Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Peking University, 100871, Beijing, China.
  • 7 Department of Gastrointestinal Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
  • 8 CAS Key Laboratory of RNA Biology; Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, China.
  • 9 Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China.
  • 10 CAS Key Laboratory of RNA Biology; Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, China. tiany@ibp.ac.cn.
  • 11 Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China. jmying@cicams.ac.cn.
  • # Contributed equally.
PMID: 32367039 DOI: 10.1038/s41422-020-0312-y
Abstract

Innate lymphoid cells (ILCs) reside in mucosal surfaces to potentiate immune responses, sustain mucosal integrity and maintain tissue homeostasis. However, how tumor infiltrating ILCs modulate tumor development and progression is unclear. Here we profiled tumor infiltrating ILCs during colorectal Cancer (CRC) progression by single-cell RNA Sequencing. We identified six clusters of tumor infiltrating ILCs with unique features. ILC1s expressed inhibitory receptors and underwent inhibitory functional conversion at the late stage of CRC. ILC2s were classified into three subsets (called ILC2-A, -B, -C), of which ILC2-C subset could facilitate tumor progression. HS3ST1 and PD1 were highly expressed in ILC2s of late stage CRC tumors and deficiency of HS3ST1 or PD1 in ILC2s suppressed tumor growth. Moreover, ILC3s transdifferentiated into ILCregs during CRC progression and ILCregs promoted tumor growth. Of note, TGF-β signaling initiated the conversion of ILC3s to ILCregs and blockade of TGF-β signaling could disrupt the ILCreg transdifferentiation and inhibited tumor growth. Thus, intervention of ILC conversions might be a potential strategy for CRC immunotherapy.

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