Liao Yunxi, Wu Chenyang, Li Yang, Wen Jinhua, Zhao Dongyu
Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China.
iScience. 2023 Jul 2;26(8):107273. doi: 10.1016/j.isci.2023.107273. eCollection 2023 Aug 18.
Immunotherapy targeting tumor-associated macrophages (TAMs) is a promising approach to treating cancer. However, the limited drug targets and ambiguous mechanisms impede the development of clinical immunotherapy strategies. To elucidate the underlying processes involved in mononuclear phagocyte (MNP) infiltration and phenotypic changes in hepatocellular carcinoma (HCC), we integrated single-cell RNA-sequencing data from 100,030 cells derived from patients with HCC and healthy individuals and compared the phenotypes and origins of the MNPs in the tumor core, tumor periphery, adjacent normal tissue, and healthy liver samples. Using machine learning and multi-omics analyses, we identified 445 infiltration-associated genes and potential drug targets affecting this process. Through experiments, we found that the expression of macrophage migration inhibitory factor (MIF) is the upstream regulator of secreted phosphoprotein 1 (SPP1) and promote migration in TAMs. Our findings also indicate that MIF promotes tumor metastasis and invasion and is a promising potential target for treating HCC.
靶向肿瘤相关巨噬细胞（TAM）的免疫疗法是一种很有前景的癌症治疗方法。然而，有限的药物靶点和模糊的机制阻碍了临床免疫治疗策略的发展。为了阐明肝细胞癌（HCC）中单核吞噬细胞（MNP）浸润和表型变化所涉及的潜在过程，我们整合了来自HCC患者和健康个体的100,030个细胞的单细胞RNA测序数据，并比较了肿瘤核心、肿瘤周边、相邻正常组织和健康肝脏样本中MNP的表型和来源。通过机器学习和多组学分析，我们确定了445个与浸润相关的基因和影响这一过程的潜在药物靶点。通过实验，我们发现巨噬细胞迁移抑制因子（MIF）的表达是分泌性磷蛋白1（SPP1）的上游调节因子，并促进TAM中的迁移。我们的研究结果还表明，MIF促进肿瘤转移和侵袭，是治疗HCC的一个有前景的潜在靶点。
