Evidence map›Paper›PMID 42686372›Full record

ArticleJournal for immunotherapy of cancer2026

LIM and SH3 protein 1 deficiency confers resistance to cytotoxic lymphocyte-mediated lysis and immunotherapy in gastric cancer by disrupting cytoskeleton dynamics.

Teming Zhang, Yingying Sun, Chao Chen, Jingwei Zheng, Liyun Chang, Yizhen Xiang, Qiongying Zhang, Haoliang Li, Wangkai Xie, Qiaoyi Xu and 6 more

Abstract read
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.

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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

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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

16 authors.

Teming Zhang *NHC Key Laboratory of Clinical Nutrition and Intervention, Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, Department of Oncology, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.ORCID http://orcid.org/0009-0006-6144-4109
Yingying Sun *Wenzhou Key Laboratory of Cancer-related Pathogens and Immunity, Zhejiang International Cooperation Base for Tumor-Associated Pathogen and Host Interaction, Institute of Molecular Virology and Immunology, Department of Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Chao Chen *NHC Key Laboratory of Clinical Nutrition and Intervention, Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, Department of Oncology, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Jingwei Zheng *NHC Key Laboratory of Clinical Nutrition and Intervention, Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, Department of Oncology, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Liyun ChangNHC Key Laboratory of Clinical Nutrition and Intervention, Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, Department of Oncology, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Yizhen XiangWenzhou Key Laboratory of Cancer-related Pathogens and Immunity, Zhejiang International Cooperation Base for Tumor-Associated Pathogen and Host Interaction, Institute of Molecular Virology and Immunology, Department of Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Qiongying ZhangDepartment of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Haoliang LiNHC Key Laboratory of Clinical Nutrition and Intervention, Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, Department of Oncology, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Wangkai XieNHC Key Laboratory of Clinical Nutrition and Intervention, Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, Department of Oncology, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Qiaoyi XuCixi Biomedical Research Institute, Wenzhou Medical University, Ningbo, Zhejiang, China.
Chenchen MaoWenzhou Key Laboratory of Cancer-related Pathogens and Immunity, Zhejiang International Cooperation Base for Tumor-Associated Pathogen and Host Interaction, Institute of Molecular Virology and Immunology, Department of Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Mingdong LuInternational Science and Technology Cooperation Base for Tumor Translational Research of Zhejiang Province, Department of Gastrointestinal Surgery, Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Zhenzhai CaiInternational Science and Technology Cooperation Base for Tumor Translational Research of Zhejiang Province, Department of Gastrointestinal Surgery, Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China hanzheng@wmu.edu.cn wzxxy@wmu.edu.cn 13968888872@163.com caizhenzhai@wmu.edu.cn.
Xian ShenNHC Key Laboratory of Clinical Nutrition and Intervention, Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, Department of Oncology, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China hanzheng@wmu.edu.cn wzxxy@wmu.edu.cn 13968888872@163.com caizhenzhai@wmu.edu.cn.
Xiangyang XueWenzhou Key Laboratory of Cancer-related Pathogens and Immunity, Zhejiang International Cooperation Base for Tumor-Associated Pathogen and Host Interaction, Institute of Molecular Virology and Immunology, Department of Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China hanzheng@wmu.edu.cn wzxxy@wmu.edu.cn 13968888872@163.com caizhenzhai@wmu.edu.cn.
Zheng HanNHC Key Laboratory of Clinical Nutrition and Intervention, Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, Department of Oncology, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China hanzheng@wmu.edu.cn wzxxy@wmu.edu.cn 13968888872@163.com caizhenzhai@wmu.edu.cn.ORCID http://orcid.org/0009-0009-7942-1505

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundA substantial amount of research has been dedicated to the mechanisms by which tumor cells evade immune system recognition and manipulate the immune microenvironment to facilitate immune escape. Recent studies have shown that viruses and tumors can protect themselves from immune cytotoxicity by remodeling the actin cytoskeleton. However, cytoskeleton-mediated immune resistance and the specific cytoskeleton-related proteins involved require further research.

methodsSingle-cell RNA sequencing was used to identify cytoskeleton-related genes associated with the response to anti-programmed cell death protein 1 (PD-1) therapy across four digestive tumors. Immunohistochemistry was used to detect LASP1 expression in gastric cancer and analyze its prognostic value for survival and anti-PD-1 response. The impact of LASP1 deficiency on tumor response to anti-PD-1 treatment and cytotoxic lymphocyte-mediated lysis was determined in vivo and in vitro. Live-cell imaging was used to compare actin cytoskeletal dynamics at the immunological synapse between LASP1-deficient and mock tumor cells. Molecular mechanisms underlying LASP1-mediated immune-resistance were dissected using co-immunoprecipitation, immunofluorescence, domain deletion complementation, and Laurdan staining.

resultsThe deficiency of LASP1 in gastric cancer affected the sensitivity of tumor cells to immunotherapy and induced cytotoxic lymphocytes exhaustion. LASP1 may act as a scaffold protein to regulate the Arp2/3 complex and remodel the cytoskeleton at the immunological synapses. LASP1 deficiency in tumor cells impairs lytic immunological synapse function by disrupting cytoskeletal dynamics-mediated cell membrane lipid organization at the immunological synapse. Finally, simvastatin combined with anti-PD-1 therapy reversed immunotherapy resistance in LASP1-deficient tumors.

conclusionsThe deficiency of LASP1 in tumors mediates immunological synapse dysfunction by affecting cytoskeletal dynamics-mediated cell membrane lipid organization, thus enabling tumors to protect themselves from immune cytotoxicity and immunotherapy.

Indexed as

Adaptor Proteins, Signal TransducingCytoskeletal ProteinsCytoskeletonImmunotherapyLIM Domain ProteinsStomach NeoplasmsT-Lymphocytes, CytotoxicAnimalsCell Line, TumorFemaleHumansMiceAdaptor Proteins, Signal TransducingCytoskeletal ProteinsLASP1 protein, humanLIM Domain ProteinsEscape/evasionGastric CancerImmunotherapy

Identifiers

PMID42686372
PMCPMC13548228

What Socratic holds

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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.