Evidence map›Paper›PMID 41085544›Full record

ArticleHepatology communications2025

HMOX1+ macrophages determine immunosuppressive microenvironment and immunotherapy efficacy in hepatocellular carcinoma.

Yabing Du, Wenxin Xu, Zhenkun Liu, Peihao Wen, Ruifeng Song, Weiwei Hao, Yating Liu, Xinlei Zhao, Meiying Gu, Jialei Weng and 1 more

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Article in Hepatology communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Yabing DuDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China.
Wenxin XuDepartment of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, P.R. China.
Zhenkun LiuDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China.
Peihao WenDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, P.R. China.
Ruifeng SongDepartment of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China.
Weiwei HaoDepartment of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China.
Yating LiuDepartment of Ophthalmology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
Xinlei ZhaoInstitute for Pathology, University Hospital of Cologne, Cologne, Germany.
Meiying GuDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China.
Jialei WengDepartment of Surgical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.ORCID 0000-0002-4916-0799
Wei HeDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHCC is a notably immunosuppressive malignancy with limited therapeutic options and poor prognosis. Macrophages, as major immune cell populations within the tumor microenvironment, significantly influence disease progression and therapy efficacy. We aim to identify pivotal macrophage subsets associated with HCC progression and resistance to immunotherapy.

methodsImmunotherapy-associated macrophage-specific marker genes were identified by single-cell RNA-sequencing analysis and transcriptome analysis. The clinical relevance of macrophages with heme oxygenase 1 (HMOX1) positive was assessed in HCC patients by immunofluorescence. The immune microenvironment of HCC and the functional phenotype of HMOX1+ macrophages were explored using cytometry by time-of-flight (CyTOF).

resultsSingle-cell RNA-sequencing analyses revealed that HMOX1 was predominantly expressed in intratumoral macrophages within the HCC microenvironment. Intratumoral HMOX1+ macrophages abundance was associated with worse prognosis and immunotherapy efficacy in patients with HCC. CyTOF analysis showed that the HCC microenvironment with high infiltration of HMOX1+ macrophages was characterized by high infiltration of CD4+ regulatory T cells (Tregs) and high expression of programmed death-1 (PD-1) in CD8+ T cells. Besides, HMOX1+ macrophages exhibited an immunosuppressive functional state. Pharmacological inhibition of HMOX1 by Znpp enhanced the therapeutic efficacy of anti-PD-1 antibody in the HCC mouse model.

conclusionsMacrophage-specific HMOX1 serves as a novel biomarker for predicting the efficacy of immunotherapy, and targeting HMOX1 has the potential to enhance the efficacy of anti-PD-1 therapy in HCC patients.

Indexed as

Carcinoma, HepatocellularHeme Oxygenase-1ImmunotherapyLiver NeoplasmsMacrophagesTumor MicroenvironmentAnimalsFemaleHumansMaleMiceProgrammed Cell Death 1 ReceptorT-Lymphocytes, RegulatoryTumor-Associated MacrophagesHeme Oxygenase-1HMOX1 protein, humanPDCD1 protein, humanProgrammed Cell Death 1 ReceptorHCCheme oxygenase-1immunotherapymacrophagestumor microenvironment

Identifiers

PMID41085544
PMCPMC12520218

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