Evidence map›Paper›PMID 42169077›Full record

ArticleMolecular cancer2026

CTHRC1 drives megakaryocyte-mediated immunotherapy resistance in esophageal squamous cell carcinoma via the integrin αIIbβ3/Rap1 pathway and is targetable by mRNA vaccination.

Yixin Liu, Jianfeng Zhou, Mengyuan Song, Jian Wang, Qixin Shang, Jiajia Du, Yanxin Li, Xiangzheng Chen, Jing Wang, Xuerui Liao and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cancer, 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

15 authors.

Yixin Liu *Department of Thoracic Surgery, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, Sichuan, China.
Jianfeng Zhou *Department of Thoracic Surgery, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, Sichuan, China.
Mengyuan Song *Department of Laboratory Medicine, Clinical Laboratory Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Jian Wang *Department of Thoracic Surgery, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, Sichuan, China.
Qixin Shang *Department of Thoracic Surgery, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, Sichuan, China.
Jiajia DuDepartment of Gastroenterology, State Key Laboratory of Biotherapy and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Yanxin LiDepartment of Gastroenterology, State Key Laboratory of Biotherapy and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Xiangzheng ChenDepartment of Liver Surgery & Liver Transplantation, West China Hospital, Sichuan University, Chengdu, Sichuan,, China.
Jing WangState Key Laboratory of Respiratory Health and Multimorbidity, School of Basic Medicine, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Xuerui LiaoDepartment of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Longqi ChenDepartment of Thoracic Surgery, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, Sichuan, China.
Weimin LiDepartment of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China. weimi003@scu.edu.cn.
Yong YuanDepartment of Thoracic Surgery, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, Sichuan, China. yongyuan@scu.edu.cn.
Yushang YangDepartment of Thoracic Surgery, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, Sichuan, China. dryangysh@scu.edu.cn.
Yangping WuDepartment of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China. yangping.wu@wcscu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The clinical efficacy of immunotherapy in advanced esophageal squamous cell carcinoma (ESCC) remains suboptimal, as most patients eventually develop drug resistance and experience disease progression. Here, we identify Collagen Triple Helix Repeat Containing 1 (CTHRC1) as a critical mediator of immunotherapy resistance in ESCC. Elevated CTHRC1 expression was observed in tumors unresponsive to immune checkpoint blockade and was associated with enhanced platelet activity and infiltration of megakaryocytes (MKs) into the tumor microenvironment. Mechanistically, CTHRC1 facilitated MK activation and recruitment, fostering an immunosuppressive niche that impaired cytotoxic T-cell activity and promoted cell exhaustion. To therapeutically target this axis, we developed a lipid nanoparticle (LNP)-encapsulated mRNA vaccine encoding CTHRC1. In preclinical ESCC models, the CTHRC1-mRNA-LNP vaccine elicited robust antitumor immunity. Notably, the combination of CTHRC1-mRNA vaccination with anti-PD-1 therapy induced synergistic intratumoral T-cell infiltration, depletion of MKs, reversal of immunosuppression, and durable tumor regression. Collectively, these findings uncover an unrecognized immunoregulatory function of CTHRC1 in ESCC and highlight its therapeutic targeting as a promising strategy to enhance the efficacy of immune checkpoint blockade.

Indexed as

Cancer VaccinesDrug Resistance, NeoplasmEsophageal NeoplasmsEsophageal Squamous Cell CarcinomaImmunotherapymRNA VaccinesAnimalsCell Line, TumorExtracellular Matrix ProteinsFemaleHumansMiceRNA, MessengerSignal TransductionTumor MicroenvironmentXenograft Model Antitumor AssaysCancer VaccinesCTHRC1 protein, humanExtracellular Matrix ProteinsmRNA VaccinesRNA, MessengerCTHRC1Esophageal squamous cell carcinomaImmunotherapy resistanceMegakaryocytesmRNA vaccine

Identifiers

PMID42169077
PMCPMC13377830

What Socratic 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 Socratic graph.