2. Academic Validation
  3. Cancer cell-expressed BTNL2 facilitates tumour immune escape via engagement with IL-17A-producing γδ T cells

Cancer cell-expressed BTNL2 facilitates tumour immune escape via engagement with IL-17A-producing γδ T cells

  • Nat Commun. 2022 Jan 11;13(1):231. doi: 10.1038/s41467-021-27936-8.
Yanyun Du # 1,  Qianwen Peng # 1,  Du Cheng 2,  Ting Pan 1,  Wanwei Sun 1,  Heping Wang 1,  Xiaojian Ma 1,  Ruirui He 1 3 4,  Huazhi Zhang 1,  Zhihui Cui 1,  Xiong Feng 1,  Zhiqiang Liu 1,  Tianxin Zhao 1,  Wenjun Hu 1,  Lei Shen 2,  Wenyang Jiang 5,  Na Gao 6,  Bradley N Martin 7,  Cun-Jin Zhang 8,  Zhanguo Zhang 9,  Chenhui Wang 10 11 12
Affiliations

Affiliations

  • 1 Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, 430074, Wuhan, China.
  • 2 Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China.
  • 3 The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, 611731, Chengdu, China.
  • 4 Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.
  • 5 Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
  • 6 Key Laboratory of Molecular Biophysics of the Ministry of Education, Hubei Key Laboratory of Bioinformatics and Molecular-imaging, Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, 430074, Wuhan, China.
  • 7 Division of pulmonary and critical care medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • 8 Department of Neurology of Drum Tower Hospital, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu, China.
  • 9 Department of Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430070, Wuhan, China.
  • 10 Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, 430074, Wuhan, China. wangchenhui@hust.edu.cn.
  • 11 The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, 611731, Chengdu, China. wangchenhui@hust.edu.cn.
  • 12 Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China. wangchenhui@hust.edu.cn.
  • # Contributed equally.
PMID: 35017553 DOI: 10.1038/s41467-021-27936-8
Abstract

Therapeutic blockade of the Immune Checkpoint Proteins programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA4) has transformed Cancer treatment. However, the overall response rate to these treatments is low, suggesting that immune checkpoint activation is not the only mechanism leading to dysfunctional anti-tumour immunity. Here we show that butyrophilin-like protein 2 (BTNL2) is a potent suppressor of the anti-tumour immune response. Antibody-mediated blockade of BTNL2 attenuates tumour progression in multiple in vivo murine tumour models, resulting in prolonged survival of tumour-bearing mice. Mechanistically, BTNL2 interacts with local γδ T cell populations to promote IL-17A production in the tumour microenvironment. Inhibition of BTNL2 reduces the number of tumour-infiltrating IL-17A-producing γδ T cells and myeloid-derived suppressor cells, while facilitating cytotoxic CD8+ T cell accumulation. Furthermore, we find high BTNL2 expression in several human tumour samples from highly prevalent Cancer types, which negatively correlates with overall patient survival. Thus, our results suggest that BTNL2 is a negative regulator of anti-tumour immunity and a potential target for Cancer Immunotherapy.

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