肿瘤相关巨噬细胞(TAM)是肿瘤微环境(TME)中数量最多的免疫细胞群体，对肿瘤发展和治疗抵抗具有关键作用。根据不同的极化状态，TAMs也可以诱导抗肿瘤免疫应答或免疫抑制。本研究确认了Jumonji结构域含有6号(JMJD6)的功能为TAM激活的新调节因子，并且其上调与TAMs的免疫抑制活性有关。JMJD6缺失减弱了Lewis肺癌(LLC)和B16F10黑素瘤的生长，通过逆转巨噬细胞的M2样激活状态，并增强了瘤细胞对免疫检查点抑制剂(ICB)的敏感性。此外，JMJD6诱导的M2极化抑制可能通过STAT3/IL-10信号传导介导。这些发现强调了JMJD6在TAM极化中的调控活性以及JMJD6/STAT3/IL-10轴抑制对增强ICB在肿瘤治疗中的疗效有潜在的治疗潜力。© 2023. 作者。

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.© 2023. The Author(s).