JMJD6 in tumor-associated macrophage regulates macrophage polarization and cancer progression via STAT3/IL-10 axis

作者：Siyuan Chen, Manni Wang, Tianqi Lu, Yu Liu, Weiqi Hong, Xuemei He, Yuan Cheng, Jian Liu, Yuquan Wei, Xiawei Wei · 发表于：Oncogene · 年份：2023 · DOI：10.1038/s41388-023-02781-9 · 被引用次数：81 · 研究领域：Immune cells in cancer、Histone Deacetylase Inhibitors Research、Cancer Immunotherapy and Biomarkers

The tumor-associated macrophage (TAM) is the most abundant group of immune cells in the tumor microenvironment (TME), which plays a critical role in the regulation of tumor progression and treatment resistance. Based on different polarization status, TAMs may also induce antitumor immune responses or immunosuppression. The present study identified JMJD6 (Jumonji domain-containing 6) as a novel modulator of TAM activation, the upregulation of which was associated with the immunosuppressive activities of TAMs. JMJD6 deficiency attenuated the growth of both Lewis lung carcinoma (LLC) tumors and B16F10 melanomas by reversing M2-like activation of macrophages, and sensitized tumors to immune checkpoint blockades (ICBs). Moreover, the JMJD6-induced inhibition of M2 polarization was potentially mediated by the STAT3/IL-10 signaling. These findings highlight the regulatory activities of JMJD6 in TAM polarization, and the therapeutic potential of JMJD6/STAT3/IL-10 axis blockades to enhance the efficacy of ICBs in cancer treatment.