. 2020 Jun;22(6):716-727.

doi: 10.1038/s41556-020-0510-3. Epub 2020 May 4.

Myeloid PTEN promotes chemotherapy-induced NLRP3-inflammasome activation and antitumour immunity

Yi Huang^{1

2}, Huanyu Wang¹, Yize Hao¹, Hualong Lin¹, Menghao Dong^{3

4}, Jin Ye¹, Lei Song⁵, Yunzhi Wang⁶, Qingqing Li⁷, Benjie Shan⁴, Yizhou Jiang^{8

9}, Hongqi Li¹⁰, Zhiming Shao^{8

9}, Guido Kroemer^{7

11

12

13

14

15

16

17}, Huafeng Zhang¹, Li Bai¹, Tengchuan Jin¹, Chao Wang¹, Yuting Ma^{7

18}, Yongping Cai¹⁹, Chen Ding⁶, Suling Liu²⁰, Yueyin Pan²¹, Wei Jiang²², Rongbin Zhou^{23

24}

Affiliations

¹ Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
² CAS Centre for Excellence in Cell and Molecular Biology, University of Science and Technology of China, Hefei, China.
³ Wannan Medical College, Wuhu, China.
⁴ Department of Oncology, the First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
⁵ National Center for Protein Sciences (Beijing), State Key Laboratory of Proteomics, Institute of Lifeomics, Beijing, China.
⁶ State Key Laboratory of Genetic Engineering, Human Phenome Institute, Institutes of Biomedical Sciences, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.
⁷ Suzhou Institute of Systems Medicine, Suzhou, China.
⁸ Fudan University Shanghai Cancer Center & Institutes of Biomedical Sciences, Shanghai Medical College, Key Laboratory of Breast Cancer in Shanghai, Innovation Center for Cell Signaling Network, Cancer Institute, Fudan University, Shanghai, China.
⁹ Department of Oncology, Department of Breast Surgery, Shanghai Medical College, Fudan University, Shanghai, China.
¹⁰ Fudan University Zhongshan Hospital, Shanghai Medical College, Shanghai, China.
¹¹ Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
¹² Equipe 11 Labellisée Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France.
¹³ Institut National de la Santé et de la Recherche Médicale, Paris, France.
¹⁴ Université Pierre et Marie Curie, Paris, France.
¹⁵ Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France.
¹⁶ Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
¹⁷ Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.
¹⁸ Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
¹⁹ Department of Pathology, Anhui Medical University, Hefei, China.
²⁰ Fudan University Shanghai Cancer Center & Institutes of Biomedical Sciences, Shanghai Medical College, Key Laboratory of Breast Cancer in Shanghai, Innovation Center for Cell Signaling Network, Cancer Institute, Fudan University, Shanghai, China. suling@fudan.edu.cn.
²¹ Department of Oncology, the First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. panyueyin@ustc.edu.cn.
²² Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. ustcjw@ustc.edu.cn.
²³ Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. zrb1980@ustc.edu.cn.
²⁴ CAS Centre for Excellence in Cell and Molecular Biology, University of Science and Technology of China, Hefei, China. zrb1980@ustc.edu.cn.

PMID: 32367047
DOI: 10.1038/s41556-020-0510-3

Myeloid PTEN promotes chemotherapy-induced NLRP3-inflammasome activation and antitumour immunity

Yi Huang et al. Nat Cell Biol. 2020 Jun.

. 2020 Jun;22(6):716-727.

doi: 10.1038/s41556-020-0510-3. Epub 2020 May 4.

Authors

Affiliations

¹ Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
² CAS Centre for Excellence in Cell and Molecular Biology, University of Science and Technology of China, Hefei, China.
³ Wannan Medical College, Wuhu, China.
⁴ Department of Oncology, the First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
⁵ National Center for Protein Sciences (Beijing), State Key Laboratory of Proteomics, Institute of Lifeomics, Beijing, China.
⁶ State Key Laboratory of Genetic Engineering, Human Phenome Institute, Institutes of Biomedical Sciences, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.
⁷ Suzhou Institute of Systems Medicine, Suzhou, China.
⁸ Fudan University Shanghai Cancer Center & Institutes of Biomedical Sciences, Shanghai Medical College, Key Laboratory of Breast Cancer in Shanghai, Innovation Center for Cell Signaling Network, Cancer Institute, Fudan University, Shanghai, China.
⁹ Department of Oncology, Department of Breast Surgery, Shanghai Medical College, Fudan University, Shanghai, China.
¹⁰ Fudan University Zhongshan Hospital, Shanghai Medical College, Shanghai, China.
¹¹ Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
¹² Equipe 11 Labellisée Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France.
¹³ Institut National de la Santé et de la Recherche Médicale, Paris, France.
¹⁴ Université Pierre et Marie Curie, Paris, France.
¹⁵ Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France.
¹⁶ Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
¹⁷ Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.
¹⁸ Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
¹⁹ Department of Pathology, Anhui Medical University, Hefei, China.
²⁰ Fudan University Shanghai Cancer Center & Institutes of Biomedical Sciences, Shanghai Medical College, Key Laboratory of Breast Cancer in Shanghai, Innovation Center for Cell Signaling Network, Cancer Institute, Fudan University, Shanghai, China. suling@fudan.edu.cn.
²¹ Department of Oncology, the First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. panyueyin@ustc.edu.cn.
²² Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. ustcjw@ustc.edu.cn.
²³ Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. zrb1980@ustc.edu.cn.
²⁴ CAS Centre for Excellence in Cell and Molecular Biology, University of Science and Technology of China, Hefei, China. zrb1980@ustc.edu.cn.

PMID: 32367047
DOI: 10.1038/s41556-020-0510-3

Abstract

PTEN is a dual-specificity phosphatase that is frequently mutated in human cancer, and its deficiency in cancer has been associated with therapy resistance and poor survival. Although the intrinsic tumour-suppressor function of PTEN has been well established, evidence of its role in the tumour immune microenvironment is lacking. Here, we show that chemotherapy-induced antitumour immune responses and tumour suppression rely on myeloid-cell PTEN, which is essential for chemotherapy-induced activation of the NLRP3 inflammasome and antitumour immunity. PTEN directly interacts with and dephosphorylates NLRP3 to enable NLRP3-ASC interaction, inflammasome assembly and activation. Importantly, supplementation of IL-1β restores chemotherapy sensitivity in mouse myeloid cells with a PTEN deficiency. Clinically, chemotherapy-induced IL-1β production and antitumour immunity in patients with cancer is correlated with PTEN expression in myeloid cells, but not tumour cells. Our results demonstrate that myeloid PTEN can determine chemotherapy responsiveness by promoting NLRP3-dependent antitumour immunity and suggest that myeloid PTEN might be a potential biomarker to predict chemotherapy responses.

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Myeloid PTEN promotes chemotherapy-induced NLRP3-inflammasome activation and antitumour immunity

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Myeloid PTEN promotes chemotherapy-induced NLRP3-inflammasome activation and antitumour immunity

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