Department of General Surgery, NO.215 Hospital of Shaanxi Nuclear Industry, #35 Weiyang West Road, Xianyang, Shaanxi, 712000, China.
Department of General Surgery, NO.215 Hospital of Shaanxi Nuclear Industry, #35 Weiyang West Road, Xianyang, Shaanxi, 712000, China.
Biochem Biophys Res Commun. 2022 Dec 25;636(Pt 1):140-146. doi: 10.1016/j.bbrc.2022.10.079. Epub 2022 Oct 25.
Triggering receptor expressed on myeloid cells 2 (TREM2), which is typically expressed in microglia/macrophage, is a crucial receptor modulating the activation of immune cells. Recent single-cell RNA sequencing studies of the tumor microenvironment (TME) have found that TREM2 is highly expressed in several subgroups of tumor-associated macrophages (TAMs) with immunosuppressive activity. TREM2 knockout mice are more resistant to tumor growth than wild-type mice in multiple mice tumor models. But the function of TREM2 expression in TAMs of hepatocellular carcinoma (HCC) is still unclear. Here we used a self-complementary adeno-associated virus (scAAV) with macrophage tropism to efficiently knockdown TREM2 in TAMs in vivo and found that the growth of hepatocellular carcinoma was suppressed by TREM2 knockdown. Moreover, we found that TREM2 knockdown remodeled TAMs to an immune-stimulating status and enhanced the therapeutic effect of PD-1 immune-checkpoint blockade in HCC.
髓系细胞触发受体 2（TREM2）通常在小胶质细胞/巨噬细胞中表达，是一种调节免疫细胞激活的关键受体。最近对肿瘤微环境（TME）的单细胞 RNA 测序研究发现，TREM2 在具有免疫抑制活性的几种肿瘤相关巨噬细胞（TAM）亚群中高度表达。在多种小鼠肿瘤模型中，TREM2 敲除小鼠比野生型小鼠更能抵抗肿瘤生长。但是，TREM2 在肝癌（HCC）TAM 中的表达功能尚不清楚。在这里，我们使用具有巨噬细胞趋向性的自我互补腺相关病毒（scAAV）在体内有效地敲低 TAMs 中的 TREM2，发现 TREM2 敲低抑制了肝癌的生长。此外，我们发现 TREM2 敲低将 TAMs 重塑为免疫刺激状态，并增强了 HCC 中 PD-1 免疫检查点阻断的治疗效果。
