Evidence map›Paper›PMID 42157270›Full record

ArticleJournal of experimental & clinical cancer research : CR2026

Targeting immunoglobulin superfamily member 9 (IGSF9) to overcome acute myeloid leukemia resistance to CAR-T therapy.

Xianhui Meng, Fangmin Li, Hong Yu, Chunling Li, Yuxiao Sun, Hongying Wang, Guantong Liu, Jiashen Zhang, Lijun Hui, Fang Li and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 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
–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

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

13 authors.

Xianhui Meng *Shandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medicine and Health Key Lab of Respiratory Infection and Tumor Immunity, Department of Biochemistry and Molecular Biology, Shandong Tumour Immunotherapy Research Innovation Team, Shandong Medical And Pharmaceutical University, Yantai, Shandong, 264003, P.R. China. xianhm@bzmc.edu.cn.
Fangmin Li *Shandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medicine and Health Key Lab of Respiratory Infection and Tumor Immunity, Department of Biochemistry and Molecular Biology, Shandong Tumour Immunotherapy Research Innovation Team, Shandong Medical And Pharmaceutical University, Yantai, Shandong, 264003, P.R. China.
Hong Yu *Shandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medicine and Health Key Lab of Respiratory Infection and Tumor Immunity, Department of Biochemistry and Molecular Biology, Shandong Tumour Immunotherapy Research Innovation Team, Shandong Medical And Pharmaceutical University, Yantai, Shandong, 264003, P.R. China.
Chunling LiShandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medicine and Health Key Lab of Respiratory Infection and Tumor Immunity, Department of Biochemistry and Molecular Biology, Shandong Tumour Immunotherapy Research Innovation Team, Shandong Medical And Pharmaceutical University, Yantai, Shandong, 264003, P.R. China.
Yuxiao SunShandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medicine and Health Key Lab of Respiratory Infection and Tumor Immunity, Department of Biochemistry and Molecular Biology, Shandong Tumour Immunotherapy Research Innovation Team, Shandong Medical And Pharmaceutical University, Yantai, Shandong, 264003, P.R. China.
Hongying WangShandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medicine and Health Key Lab of Respiratory Infection and Tumor Immunity, Department of Biochemistry and Molecular Biology, Shandong Tumour Immunotherapy Research Innovation Team, Shandong Medical And Pharmaceutical University, Yantai, Shandong, 264003, P.R. China.
Guantong LiuDepartment of Thoracic Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou University Medical College, Shantou, Guangdong, 515041, P.R. China.
Jiashen ZhangShandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medicine and Health Key Lab of Respiratory Infection and Tumor Immunity, Department of Biochemistry and Molecular Biology, Shandong Tumour Immunotherapy Research Innovation Team, Shandong Medical And Pharmaceutical University, Yantai, Shandong, 264003, P.R. China.
Lijun HuiShandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medicine and Health Key Lab of Respiratory Infection and Tumor Immunity, Department of Biochemistry and Molecular Biology, Shandong Tumour Immunotherapy Research Innovation Team, Shandong Medical And Pharmaceutical University, Yantai, Shandong, 264003, P.R. China.
Fang LiShandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medicine and Health Key Lab of Respiratory Infection and Tumor Immunity, Department of Biochemistry and Molecular Biology, Shandong Tumour Immunotherapy Research Innovation Team, Shandong Medical And Pharmaceutical University, Yantai, Shandong, 264003, P.R. China.
Shuping WeiShandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medicine and Health Key Lab of Respiratory Infection and Tumor Immunity, Department of Biochemistry and Molecular Biology, Shandong Tumour Immunotherapy Research Innovation Team, Shandong Medical And Pharmaceutical University, Yantai, Shandong, 264003, P.R. China.
Yaopeng WangDepartment of Thoracic Surgery, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, Shandong, 266011, P.R. China. qdwangyaopeng@163.com.
Zunling LiShandong Key Lab of Complex Medical Intelligence and Aging, Shandong Medicine and Health Key Lab of Respiratory Infection and Tumor Immunity, Department of Biochemistry and Molecular Biology, Shandong Tumour Immunotherapy Research Innovation Team, Shandong Medical And Pharmaceutical University, Yantai, Shandong, 264003, P.R. China. lizunling@bzmc.edu.cn.

Funding

National Natural Science Foundation of China 82150101, 81872332, 82070225Shandong Natural Science Foundation ZR2023QC190Shandong Natural Science Foundation ZR2024LZL010
6 · The paper itself

Abstract

backgroundCAR-T cell therapy faces substantial barriers in AML, yet the mechanisms by which AML evades CAR-T cell cytotoxicity-through tumor-intrinsic factors and microenvironmental suppression-remain poorly defined. IGSF9 has recently been identified as an immunosuppressive molecule selectively expressed on AML blasts, but its role in mediating resistance to CAR-T therapy is unknown.

methodsWe examined IGSF9 expression in AML cells upon CAR-T challenge and conducted in vitro and in vivo assays to define its functional impact on CAR-T cell activity. To overcome IGSF9-mediated suppression, we evaluated two therapeutic strategies: antibody-mediated IGSF9 blockade and the generation of IGSF9-specific CAR-T cells (IG9BBz).

resultsCAR-T-induced cytotoxic pressure upregulated IGSF9 on AML cells. IGSF9-positive AML cells exhibited resistance to CAR-T killing and impaired CAR-T persistence both in vitro and in vivo. Antibody blockade of IGSF9 restored CAR-T function in xenograft models. Moreover, IG9BBz CAR-T cells demonstrated potent and selective elimination of IGSF9-positive AML cells in both settings.

conclusionsOur findings identify a cytokine-driven IGSF9 resistance circuit that suppresses CAR-T cell function in AML. Therapeutic disruption of this pathway through IGSF9 blockade or IGSF9-specific CAR-T cells restores antitumor immunity and provides complementary strategies to overcome CAR-T resistance in AML.

Indexed as

ImmunoglobulinsImmunotherapy, AdoptiveLeukemia, Myeloid, AcuteReceptors, Chimeric AntigenAnimalsCell Line, TumorDrug Resistance, NeoplasmHumansMiceXenograft Model Antitumor AssaysImmunoglobulinsReceptors, Chimeric AntigenAMLCAR-TIGSF9Immune suppression

Identifiers

PMID42157270
PMCPMC13352843

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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.