巨噬细胞中 OIT3 的增加通过 NF-κB 信号通路促进 PD-L1 表达和肝细胞癌发生。
Increased OIT3 in macrophages promotes PD-L1 expression and hepatocellular carcinogenesis via NF-κB signaling.
机构信息
The Second Affiliated Hospital & Yuying Children's Hospital/The Second School of Medicine, Wenzhou Medical University, Wenzhou, China.
Department of Pathology, The 958th Hospital, Southwest Hospital, Army Medical University, Chongqing 400038, China.
出版信息
Exp Cell Res. 2023 Jul 15;428(2):113651. doi: 10.1016/j.yexcr.2023.113651. Epub 2023 May 16.
Oncoprotein-induced transcript 3 (OIT3) facilitates macrophage M2 polarization and hepatocellular carcinoma (HCC) progression, however, whether OIT3 regulates tumor immunity remains largely unknown. Here we found that OIT3 was upregulated in HCC-associated macrophages, which inhibited CD4 and CD8 T-cell infiltration in the tumor microenvironment (TME). Mechanistically, OIT3 increased the expression of PD-L1 on tumor-associated macrophages (TAMs) by activating NF-κB signaling, blockade of NF-κB reversed the immunosuppressive activity of TAMs and dampens HCC tumorigenesis. Our findings provide the molecular basis for OIT3 enhancing tumor immunosuppression and highlighted a potential therapeutic strategy for targeting the TAMs of HCC.
癌蛋白诱导转录物 3（OIT3）促进巨噬细胞 M2 极化和肝细胞癌（HCC）进展，然而，OIT3 是否调节肿瘤免疫仍知之甚少。在这里，我们发现 OIT3 在 HCC 相关巨噬细胞中上调，抑制肿瘤微环境（TME）中 CD4 和 CD8 T 细胞的浸润。在机制上，OIT3 通过激活 NF-κB 信号增加肿瘤相关巨噬细胞（TAMs）中 PD-L1 的表达，阻断 NF-κB 逆转了 TAMs 的免疫抑制活性并抑制 HCC 肿瘤发生。我们的研究结果为 OIT3 增强肿瘤免疫抑制提供了分子基础，并强调了针对 HCC TAMs 的潜在治疗策略。
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