CD74+ macrophages are associated with favorable prognosis and immune contexture in hepatocellular carcinoma.
Cancer Immunol Immunother
; 71(1): 57-69, 2022 Jan.
Article
em En
| MEDLINE
| ID: mdl-34009409
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antígenos de Diferenciação de Linfócitos B
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Antígenos de Histocompatibilidade Classe II
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Carcinoma Hepatocelular
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Neoplasias Hepáticas
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Macrófagos
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
País/Região como assunto:
Asia
Idioma:
En
Revista:
Cancer Immunol Immunother
Ano de publicação:
2022
Tipo de documento:
Article