MIF is a critical regulator of mononuclear phagocytic infiltration in hepatocellular carcinoma

Yunxi Liao; Chenyang Wu; Yang Li; Jinhua Wen; Dongyu Zhao

doi:10.1016/j.isci.2023.107273

MIF is a critical regulator of mononuclear phagocytic infiltration in hepatocellular carcinoma

iScience. 2023 Jul 2;26(8):107273. doi: 10.1016/j.isci.2023.107273. eCollection 2023 Aug 18.

Authors

Yunxi Liao^{1

2}, Chenyang Wu^{1

2}, Yang Li³, Jinhua Wen³, Dongyu Zhao^{1

2}

Affiliations

¹ Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
² State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China.
³ Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.

Abstract

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 in vitro 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.

Keywords: Cancer; Microenvironment; Transcriptomics.