Evidence map›Paper›PMID 42259604›Full record

ArticleJournal for immunotherapy of cancer2026

VSIG4 suppresses antitumor T cell immunity via the SLC3A2-dependent metabolic-ionic checkpoint.

Guoling Huang, Ruirui He, Wei Wang, Heping Wang, Yangyang Li, Bo Zeng, Panyin Shu, Ting Pan, Ming Yi, Lingyun Feng and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 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
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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

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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

17 authors.

Guoling HuangThe Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Ruirui HeThe Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China wangch@uestc.edu.cn heruirui0628@uestc.edu.cn xiaoxue@med.uestc.edu.cn wangyuan_med@uestc.edu.cn.
Wei WangThe Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Heping WangThe Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Yangyang LiThe Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Bo ZengThe Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Panyin ShuSchool of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Ting PanSchool of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Ming YiThe Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Lingyun FengThe Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Zhihui CuiThe Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Xi LiSchool of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Yanyun DuThe Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Hong JiangState Key Laboratory of Biotherapy, Department of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Xue XiaoDepartment of Pathology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China wangch@uestc.edu.cn heruirui0628@uestc.edu.cn xiaoxue@med.uestc.edu.cn wangyuan_med@uestc.edu.cn.
Yuan WangThe Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China wangch@uestc.edu.cn heruirui0628@uestc.edu.cn xiaoxue@med.uestc.edu.cn wangyuan_med@uestc.edu.cn.
Chenhui WangThe Key Laboratory for Human Disease Gene Study of Sichuan Province and the Department of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China wangch@uestc.edu.cn heruirui0628@uestc.edu.cn xiaoxue@med.uestc.edu.cn wangyuan_med@uestc.edu.cn.ORCID http://orcid.org/0000-0002-3186-3066

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BackgroundImmune checkpoint blockade therapy aims to restore T-cell function within the tumor microenvironment (TME), eliciting durable antitumor responses. However, clinical response rates to PD-1/PD-L1 inhibitors remain limited, particularly in immunologically "cold" tumors such as pancreatic cancer, underscoring the need for alternative immunotherapeutic strategies. V-set and immunoglobulin domain-containing 4 (VSIG4) has been implicated in tumor progression, but its functional role in T-cell regulation and mechanisms of tumor immune evasion remain unclear.

methodsSyngeneic tumor models and human VSIG4 knock-in mice were employed to investigate the therapeutic effect of VSIG4 blockade. Mouse-specific and human-specific neutralizing antibodies against VSIG4 were administered across multiple tumor types, including pancreatic cancer. Tumor-infiltrating immune cells were analyzed by flow cytometry and functional assays. Mechanistic studies examined the interaction between VSIG4 and solute carrier family 3 member 2 (SLC3A2) and its impact on amino acid transport, ion flux, and T-cell activation.

resultsTherapeutic blockade of VSIG4 significantly suppressed tumor growth and prolonged survival in several cancer models, with particular efficacy in pancreatic cancer. VSIG4 expression correlated with tumor aggressiveness, and its blockade reactivated CD8

conclusionsThese findings define a previously unrecognized metabolic-ionic checkpoint axis by which VSIG4 restricts T-cell activation through SLC3A2. Blockade of VSIG4 reprograms the TME and enhances antitumor immunity, highlighting VSIG4 as a promising therapeutic target, particularly in metabolically repressive tumors such as pancreatic cancer.

Indexed as

Amino Acid Transport System ASCT-LymphocytesAnimalsCell Line, TumorHumansMiceMice, Inbred C57BLTumor MicroenvironmentAmino Acid Transport System ASCAntibodyImmune Checkpoint InhibitorImmunotherapyMacrophageT cell

Identifiers

PMID42259604
PMCPMC13250229

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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 OpenQuestion graph.