Type I IFNs repolarized a CD169+ macrophage population with anti-tumor potentials in hepatocellular carcinoma
Type I IFNs repolarized a CD169+ macrophage population with anti-tumor potentials in hepatocellular carcinoma
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I 型 IFN 使 CD169 巨噬细胞群重新极化，在肝细胞癌中具有抗肿瘤潜力
DOI：
10.1016/j.ymthe.2021.09.021
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发表时间：
2022
影响因子：
12.4
通讯作者：
Yan Wu
中科院分区：
文献类型：
--
作者：
Jing Liao;Dan-Ni Zeng;Jin-Zhu Li;Qiao-Min Hua;Chun-Xia Huang;Jing Xu;Chong Wu;Limin Zheng;Wei-Ping Wen;Yan Wu
巨噬细胞是人类肝细胞癌（HCC）的主要组成部分，并发挥各种功能，促进疾病的进展。重编程或重建巨噬细胞的肿瘤监视表型代表了癌症治疗中有吸引力的免疫策略。目前的研究确定CD 169是巨噬细胞复极的潜在靶点，因为它标志着巨噬细胞群体与活化的免疫特征和HCC患者的更好预后正相关。体外实验显示，低剂量的I型干扰素（IFN）可以有效地重编程人单核细胞源性巨噬细胞以上调CD 169表达，与对照相比，这种诱导的CD 169+巨噬细胞显示出显著增强的吞噬和CD 8 +T细胞活化能力。低剂量IFNα也能抑制小鼠体内肝癌的生长，可能是通过极化CD 169+巨噬细胞群和增强CD 8 +T细胞活性。值得注意的是，IFNα还在体内诱导巨噬细胞上大量PD-L1表达，因此阻断PD-L1可以进一步增加IFNα治疗HCC的抗肿瘤功效。我们提出低剂量IFNα联合PD-L1阻断剂通过其对巨噬细胞极化的影响作为潜在的抗肿瘤治疗策略。
Macrophages constitute a major component in human hepatocellular carcinoma (HCC) and perform various functions to facilitate disease progression. Reprogramming or reconstituting the tumor surveillance phenotypes of macrophages represents an attractive immunotherapeutic strategy in cancer treatments. The current study identified CD169 as a potential target for macrophage repolarization since it signified a population of macrophages positively correlated with an activated immune signature and better prognosis of patients with HCC.In vitroexperiments revealed that a low dose of type I interferon (IFN) could effectively reprogram human monocyte-derived macrophages to upregulate CD169 expression, and such induced CD169+macrophages exhibited significantly enhanced phagocytotic and CD8+T cell-activating capacities compared to controls. A low dose of IFNα also inhibited hepatoma growth in micein vivo, presumably through polarizing the CD169+macrophage population and enhancing CD8+T cell activities. Notably, IFNα also induced substantial PD-L1 expression on macrophagesin vivo, and thus blockade of PD-L1 could further increase the anti-tumor efficacy of IFNα in the treatment of HCC. We propose a low dose of IFNα in combination with a PD-L1 blocking agent as a potential anti-tumor therapeutic strategy via its effects on macrophage polarization.