| Literature DB >> 32367047 |
Yi Huang1,2, Huanyu Wang1, Yize Hao1, Hualong Lin1, Menghao Dong3,4, Jin Ye1, Lei Song5, Yunzhi Wang6, Qingqing Li7, Benjie Shan4, Yizhou Jiang8,9, Hongqi Li10, Zhiming Shao8,9, Guido Kroemer7,11,12,13,14,15,16,17, Huafeng Zhang1, Li Bai1, Tengchuan Jin1, Chao Wang1, Yuting Ma7,18, Yongping Cai19, Chen Ding6, Suling Liu20, Yueyin Pan21, Wei Jiang22, Rongbin Zhou23,24.
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.Entities:
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Year: 2020 PMID： 32367047 DOI： 10.1038/s41556-020-0510-3
Source DB: PubMed Journal: Nat Cell Biol ISSN： 1465-7392 Impact factor: 28.824