Evidence map›Paper›PMID 42488674›Full record

ReviewFrontiers in immunology2026

Cholesterol metabolic rewiring shapes immune remodeling across hepatocarcinogenesis.

Wentao Ma, Fengxu Yan, Yu Cheng, Guoqing Zhang, Yanxi Mu, Zhiqiang Zhang, Xuefeng Liang, Jianxin Gan, Wenwei Yang, Weixiong Zhu and 1 more

Abstract readReview
In one paragraph

Review in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

11 authors.

Wentao Ma *The Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China.
Fengxu Yan *Nanchang University Queen Mary School, Nanchang, China.
Yu Cheng *The Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China.
Guoqing ZhangThe Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China.
Yanxi MuThe Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China.
Zhiqiang ZhangThe Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China.
Xuefeng LiangThe Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China.
Jianxin GanDepartment of General Surgery, The Second Hospital of Lanzhou University, Lanzhou, Gansu, China.
Wenwei YangZhangzhou Yuanshan Hospital, Zhangzhou, Fujian, China.
Weixiong ZhuThe Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China.
Yusheng ChengThe Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cholesterol metabolism, hepatocellular carcinoma (HCC), and the tumor immune microenvironment are increasingly recognized as interconnected drivers of metabolic dysfunction-associated steatotic liver disease/metabolic dysfunction-associated steatohepatitis-related HCC (MASLD/MASH-HCC). However, cholesterol dysregulation during hepatocarcinogenesis is often discussed as isolated pathways or single-stage events, and evidence strength differs across human HCC tissues, preclinical HCC models, and non-HCC systems. This review integrates mechanistic, spatial multi-omics, and translational evidence to highlight cholesterol dyshomeostasis as a stage- and cell-type-specific rewiring of synthesis, uptake, esterification, efflux, and conversion rather than a uniform metabolic increase. In chronic metabolic liver disease, sterol regulatory element-binding protein 2 (SREBP2)-SREBP cleavage-activating protein (SCAP) activation, impaired bile acid-farnesoid X receptor (FXR) feedback, free-cholesterol loading, and oxysterol accumulation may connect hepatocyte stress with stellate-cell activation, macrophage remodeling, inflammation, and fibrosis. During preneoplastic transition and early HCC, squalene epoxidase (SQLE), sterol O-acyltransferase 1 (SOAT1), farnesyl-diphosphate farnesyltransferase 1 (FDFT1), 24-dehydrocholesterol reductase (DHCR24), and SCAP-regulatory circuits may support membrane remodeling, oncogenic signaling, metabolic autonomy, and impaired immune surveillance, although their evidence levels vary. In advanced and metastatic HCC, spatially resolved studies suggest cholesterol-active tumor regions may be coupled to exhausted T cells, tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), extracellular vesicle signaling, and oxysterol-mediated communication. We further discuss stage-aligned diagnostic and therapeutic opportunities, proposing cholesterol metabolic rewiring as a hypothesis-generating and partially validated framework for HCC initiation, progression, recurrence, and therapeutic resistance.

Indexed as

CarcinogenesisCarcinoma, HepatocellularCholesterolLiver NeoplasmsAnimalsHumansMetabolic ReprogrammingTumor MicroenvironmentCholesterolcholesterol metabolismhepatocellular carcinomaimmunometabolismMASLD/MASH-HCCoxysterolsspatial omicstherapeutic resistancetumor immune microenvironment

Identifiers

PMID42488674
PMCPMC13388550

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.