Evidence map›Paper›PMID 41272735›Full record

ArticleCancer cell international2025

GPR34 inhibition reprograms tumor-associated macrophages and enhances the sensitivity of anti-PD-1 therapy in hepatocellular carcinoma.

Wenfeng Liu, Qiang Yu, Xinyi Liu, Feng Zhang, Qiuyu Jiang, Wenqing Tang, Ling Dong

Abstract read
In one paragraph

Article in Cancer cell international, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

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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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Association of intratumoral CD68Frontiers in immunology · 2026
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Wenfeng Liu *Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, P.R. China.
Qiang Yu *Department of Liver Surgery and Transplantation, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Fudan University, Ministry of Education, Shanghai, 200032, P.R. China.
Xinyi Liu *Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, P.R. China.
Feng ZhangDepartment of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, P.R. China.
Qiuyu JiangDepartment of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, P.R. China.
Wenqing TangDepartment of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, P.R. China.
Ling DongDepartment of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, P.R. China. dong.ling@zs-hospital.sh.cn.

Funding

the National Natural Science Foundation of China 82273027
6 · The paper itself

Abstract

backgroundMacrophage play a dual role in tumor progression. However, the mechanisms underlying tumor-associated macrophage (TAM) polarization in the hepatocellular carcinoma (HCC) microenvironment remain elusive.

methodsWe analyzed the proportions of tumor-infiltrating immune cells in The Cancer Genome Atlas Liver Hepatocellular Carcinoma cohort. Subsequently, a risk prediction model was constructed for patients with HCC. The expression patterns and clinical relevance of G protein-coupled receptor 34 (GPR34) were evaluated. The potential functions and mechanisms of GPR34 in macrophages were also investigated. Additionally, HCC mouse models were used to assess the therapeutic potential of a GPR34 inhibitor in enhancing immune checkpoint blockade (ICB) therapy.

resultsA novel prognostic prediction model based on macrophage-related genes was established to predict the outcomes of patients with HCC. In this model, GPR34 was identified as significantly upregulated and associated with a poor clinical prognosis in HCC. Mechanistically, GPR34 facilitated M2 macrophage polarization by activating the PI3K/AKT signaling axis. The pharmacological inhibition of GPR34 effectively suppressed tumor growth. Moreover, the combination of a GPR34 inhibitor with a PD-1 inhibitor demonstrated synergistic antitumor effects.

conclusionGPR34 is pivotal in driving macrophage M2 polarization, and inhibitor targeting GPR34 represents promising antitumor agent capable of augmenting the efficacy of anti-PD-1 therapy.

Indexed as

GPR34Hepatocellular carcinomaImmune checkpoint blockade

Identifiers

PMID41272735
PMCPMC12639727

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