Evidence map›Paper›PMID 41935049›Full record

ArticleNature communications2026

Inhibition of circulating glycocholic acid-regulated signaling potentiates immune checkpoint therapy in colorectal cancer.

Senlin Zhao, Jing Zhang, Yushuai Mi, Bin Quan, Zijuan Hu, Xinyang Zhong, Ye Xu, Sanjun Cai, Xinxiang Li, Ping Wei and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Compartmental pH regulation in cancer and antitumor immunity: therapeutic opportunities and challenges.Apoptosis : an international journal on programmed cell death · 2026
    Review
  2. 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

14 authors.

Senlin Zhao *Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.ORCID http://orcid.org/0000-0001-7079-0771
Jing Zhang *Department of Assisted Reproduction, the Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Yushuai Mi *Department of Gastrointestinal Surgery, The Second Qilu Hospital of Shandong University, Jinan, Shandong, China.
Bin Quan *Department of General Surgery of XuZhou Central Hospital, XuZhou Clinical School of Xuzhou Medical University, XuZhou Institute of Cardiovascular disease, XuZhou, Jiangsu, China.
Zijuan Hu *Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Xinyang Zhong *Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Ye XuDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Sanjun CaiDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Xinxiang LiDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.ORCID http://orcid.org/0000-0002-2354-4735
Ping WeiDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-9805-6330
WanJun ChenMucosal Immunology Section, NIDCR, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-9335-2114
Yuping ZhuDepartment of colorectal surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China. zhuyp@zjcc.org.cn.
Jianqiang TangDepartment of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. doc_tjq@hotmail.com.
Dawei LiDepartment of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. li_dawei@fudan.edu.cn.ORCID http://orcid.org/0000-0002-5642-4000

Funding

National Natural Science Foundation of China (National Science Foundation of China) 81972293National Natural Science Foundation of China (National Science Foundation of China) 82003088National Natural Science Foundation of China (National Science Foundation of China) 82372643
6 · The paper itself

Abstract

Serum bile acids (BAs) emerge as risk factors for cancer, but their roles in colorectal cancer (CRC) remain unclear. We show that glycocholic acid (GCA), a primary BA, is elevated in the serum of CRC patients. In a mouse CRC model, GCA promotes tumor programmed death-ligand 1 (PD-L1) expression in tumors, suppressing CD8⁺ T cell-mediated antitumor immunity and facilitating tumor growth. Mechanistically, GCA inhibits the BA receptor farnesoid X receptor (FXR), a transcriptional repressor for SRY-box transcription factor 14 (SOX14). Loss of FXR repression upregulates SOX14-mediated expression of zinc finger DHHC-type palmitoyl transferase 9 (DHHC9), thereby reducing PD-L1 palmitoylation and stabilization. Silencing SOX14 or DHHC9, or activating FXR, synergizes with anti-PD-1 therapy, reducing tumor growth in GCA-treated mice. These findings uncover a mechanism that GCA remodels the tumor microenvironment to mediate CRC resistance to immunotherapy, highlighting therapeutic opportunities targeting the FXR-PD-L1 axis in CRC patients with elevated serum GCA.

Indexed as

Colorectal NeoplasmsImmune Checkpoint InhibitorsAnimalsB7-H1 AntigenBile Acids and SaltsCD8-Positive T-LymphocytesCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansMaleMiceMice, Inbred C57BLReceptor, Farnesoid X-ActivatedReceptors, Cytoplasmic and NuclearSignal TransductionB7-H1 AntigenBile Acids and SaltsCD274 protein, humanImmune Checkpoint InhibitorsReceptor, Farnesoid X-ActivatedReceptors, Cytoplasmic and Nuclear

Identifiers

PMID41935049
PMCPMC13230736

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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 OpenQuestion graph.