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CD74+ macrophages are associated with favorable prognosis and immune contexture in hepatocellular carcinoma

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Abstract

CD74 was initially thought to participate mainly in antigen presentation as an MHC class II chaperone. Recent studies have shown that CD74 plays an important role within the cell and throughout the immune system in a wide spectrum of neoplasms. However, the role of CD74 in hepatocellular carcinoma (HCC) remains elusive. In this study, HCC tissues from Zhongshan Hospital and data from The Cancer Genome Atlas (TCGA) were obtained and analyzed. Immunohistochemistry, flow cytometry, and single-cell RNA sequencing (scRNA-seq) were performed to detect the characteristics of CD74+ cells and explore their impact on the tumor microenvironment (TME) of HCC. Our data revealed that stromal CD74+ cell enrichment was associated with favorable prognosis in patients with HCC. CD74 was abundant in a large portion of HCC specimens and prominently distributed on stromal macrophages. scRNA-seq data also indicated that the pathways related to immune response were significantly upregulated in CD74+ macrophages. High infiltration of CD74+ macrophages was associated with increased infiltration of CD8+ cytotoxic T lymphocytes (CTLs) with enhanced effector functions in HCC. Besides, blocking CD74 weakened the antitumor activity and proliferation ability of CD8+ CTLs in HCC. Our findings highlight the critical role of CD74 in HCC. New drugs and antibodies targeting CD74 may be effective strategies for HCC therapy.

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Data availability

Data are available upon reasonable request.

Change history

  • 17 April 2023

    Missing supplementary tables and figures have been included

Abbreviations

CI:

Confidence interval

CTL:

Cytotoxic T lymphocyte

GO:

Gene Ontology

GSEA:

Gene set enrichment analysis

HR:

Hazard ratio

HCC:

Hepatocellular carcinoma

OS:

Overall survival

RFS:

Recurrence-free survival

scRNA-seq:

Single-cell RNA sequencing

TCGA:

The Cancer Genome Atlas

TME:

Tumor microenvironment

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Funding

This work was supported by the Leading Investigator Program of the Shanghai municipal government (17XD1401100), the National Key Basic Research Program (973 Program; 2015CB554005) from the Ministry of Science and Technology of China, and the National Natural Science Foundation of China (81672326 and 81871928). All these study sponsors have no roles in the study design, collection, analysis and interpretation of data.

Author information

Author notes

  1. Nan Xiao and Kangshuai Li Contributed equally to this work.

Authors and Affiliations

  1. Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    Nan Xiao, Xiaodong Zhu, Bin Xu, Xuefeng Liu, Ming Lei & Hui-Chuan Sun

  2. Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, 200032, China

    Nan Xiao, Xiaodong Zhu, Bin Xu, Xuefeng Liu, Ming Lei & Hui-Chuan Sun

  3. Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Jinan, 250012, China

    Kangshuai Li

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  1. Nan Xiao
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Contributions

N Xiao and K-S Li were responsible for the acquisition, statistical analysis, and interpretation of the data, and the drafting of the manuscript. H-C Sun was responsible for the conception and design of the study, analysis and interpretation of data, drafting of the manuscript, obtainment of funding and study supervision. X-D Zhu, B Xu, X-F Liu, and M Lei were responsible for technical and material support. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hui-Chuan Sun.

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The study followed the Declaration of Helsinki and was approved by the Clinical Research Ethics Committee of Zhongshan Hospital, Fudan University.

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Xiao, N., Li, K., Zhu, X. et al. CD74+ macrophages are associated with favorable prognosis and immune contexture in hepatocellular carcinoma. Cancer Immunol Immunother 71, 57–69 (2022). https://doi.org/10.1007/s00262-021-02962-z

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