Evidence map›Paper›PMID 42248857›Full record

ArticleNature communications2026

Targeting fibroblast TXNDC5 resolves tumor desmoplasia and PD-1 resistance in colorectal cancer with mesenchymal traits.

Kai-Lin Cheng, Chih-I Chen, Shu-Han Yu, Huai-Wen Liang, Yi-Wei Tsai, Chen-Ting Hung, Yu-Shan Lin, Gang-Hui Lee, Po-Yu Chen, Ming-Jer Tang and 12 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 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

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

22 authors.

Kai-Lin ChengDepartment and Graduate Institute of Pharmacology, National Taiwan University College of Medicine, Taipei, Taiwan.
Chih-I ChenDivision of Colon and Rectal Surgery, Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
Shu-Han YuInstitute of Biotechnology, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan.
Huai-Wen LiangDivision of Cardiology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
Yi-Wei TsaiDepartment of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.ORCID http://orcid.org/0000-0001-7474-8765
Chen-Ting HungDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Yu-Shan LinDepartment and Graduate Institute of Pharmacology, National Taiwan University College of Medicine, Taipei, Taiwan.
Gang-Hui LeeInternational Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, Taiwan.
Po-Yu ChenInstitute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
Ming-Jer TangInternational Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, Taiwan.ORCID http://orcid.org/0000-0002-0883-4363
Yueh-Feng WuDepartment of Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
Sung-Jan LinDepartment of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.ORCID http://orcid.org/0000-0003-1325-3464
Jen-Kuang LeeDivision of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Linda Chia-Hui YuGraduate Institute and Department of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan.ORCID http://orcid.org/0000-0003-1461-3249
Shuei-Liong LinResearch Center for Developmental Biology & Regenerative Medicine, National Taiwan University, Taipei, Taiwan.ORCID http://orcid.org/0000-0002-1041-5571
Shih-Yu ChenInstitute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.ORCID http://orcid.org/0000-0002-7955-481X
Wen-Chih LeeInstitute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.ORCID http://orcid.org/0000-0001-6436-731X
Yung-Ming JengGraduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan.ORCID http://orcid.org/0000-0002-9986-7194
Ruby Yun-Ju HuangSchool of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.ORCID http://orcid.org/0000-0001-6376-3185
Ruey-Hwa ChenInstitute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.ORCID http://orcid.org/0000-0001-8124-5832
Ching-Chow ChenDepartment and Graduate Institute of Pharmacology, National Taiwan University College of Medicine, Taipei, Taiwan.ORCID http://orcid.org/0000-0002-7810-0939
Kai-Chien YangDepartment and Graduate Institute of Pharmacology, National Taiwan University College of Medicine, Taipei, Taiwan. kcyang@ntu.edu.tw.ORCID http://orcid.org/0000-0002-9128-9166

Funding

Academia Sinica IBMS-CRC111-P01, AS-TM-113-01-02 and AS-GC-110-L06National Taiwan University Hospital (NTUH) NTUH. VN112-06, VN-113-03, 112-S0307, 112-S0311, 113-S0196, 113-IF0002, 113-E0008National Taiwan University (NTU) 112L7849, 113L7832NTU | College of Medicine, National Taiwan University (College of Medicine, National Taiwan University) 110F005-112-M2, NSCCMOH-131-41, 111C101-051, 112C101-031
6 · The paper itself

Abstract

Mesenchymal-type colorectal cancer is frequently refractory to immunotherapy, with resistance largely driven by a cancer-associated fibroblast-mediated fibrotic barrier and immune exclusion. Here, we show that TXNDC5, a protein disulfide isomerase upregulated in both human and mouse colorectal cancer-associated fibroblasts, is a critical regulator of this immunosuppressive niche. Mechanistically, TXNDC5 enhances TGFβ signaling by stabilizing the TGFβ receptor TGFBR1 in fibroblasts, thereby driving fibroblast activation and pro-tumor signaling pathways. Fibroblast-specific Txndc5 deletion attenuates tumor stiffness, decompresses tumor vessels, and reduces intratumoral hypoxia while inhibiting pro-tumorigenic inflammatory fibroblast polarization and augmenting cytotoxic T-cell recruitment. This stromal remodeling restrains tumor growth and markedly sensitizes tumors to PD-1 blockade therapy. Our findings identify the TXNDC5-TGFBR1 axis as a key orchestrator of the fibrotic shield within the malignant microenvironment and suggest that targeting TXNDC5 in fibroblasts could help overcome immunotherapy resistance in patients with mesenchymal-type colorectal cancer.

Indexed as

Colorectal NeoplasmsFibroblastsProgrammed Cell Death 1 ReceptorProtein Disulfide-IsomerasesAnimalsCancer-Associated FibroblastsCell Line, TumorDrug Resistance, NeoplasmFemaleGene Expression Regulation, NeoplasticHumansMiceMice, Inbred C57BLMice, KnockoutReceptor, Transforming Growth Factor-beta Type ISignal TransductionProgrammed Cell Death 1 ReceptorProtein Disulfide-IsomerasesReceptor, Transforming Growth Factor-beta Type ITransforming Growth Factor betaTXNDC5 protein, human

Identifiers

PMID42248857
PMCPMC13396657

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.