Journal Article

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

Chen, Ding, Bai, Li, Jiang, Wei, Jiang Yizhou, Zhou Rongbin, Li, Hongqi, Ye, Jin, Ma, Yuting, Wang, Huanyu, Song, Lei, Lin Hualong, Dong Menghao, Zhang, Huafeng, Li, Qingqing, Huang, Yi, Shan Benjie, Jin Tengchuan, Pan Yueyin, Cai Yongping, Yize, Hao, Wang, Chao, Liu Suling, Shao Zhiming, Wang, Yunzhi, Kroemer Guido

2020

Overview

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.Huang et al. show that, in response to chemotherapy, PTEN directly interacts with NLRP3 in myeloid cells to enhance inflammasome activation and antitumour immune responses.

• Publisher: Nature Publishing Group
• Subject: Biomarkers / Cancer / Cell activation / Chemotherapy / IL-1β / Immune response / Immunity / Inflammasomes / Myeloid cells / PTEN protein / Supplements / Tumors