2. Academic Validation
  3. JMJD6 in tumor-associated macrophage regulates macrophage polarization and cancer progression via STAT3/IL-10 axis

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

  • Oncogene. 2023 Aug 11. doi: 10.1038/s41388-023-02781-9.
Siyuan Chen # 1,  Manni Wang # 1,  Tianqi Lu 1,  Yu Liu 1,  Weiqi Hong 1,  Xuemei He 1,  Yuan Cheng 1,  Jian Liu 1,  Yuquan Wei 1,  Xiawei Wei 2
Affiliations

Affiliations

  • 1 Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No.17, Block3, Southern Renmin Road, Chengdu, Sichuan, 610041, People's Republic of China.
  • 2 Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No.17, Block3, Southern Renmin Road, Chengdu, Sichuan, 610041, People's Republic of China. xiaweiwei@scu.edu.cn.
  • # Contributed equally.
PMID: 37567973 DOI: 10.1038/s41388-023-02781-9
Abstract

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.

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