Evidence map›Paper›PMID 39983717›Full record

ArticleCell reports. Medicine2025

Methionine intervention induces PD-L1 expression to enhance the immune checkpoint therapy response in MTAP-deleted osteosarcoma.

Haoran Mu, Qi Zhang, Dongqing Zuo, Jinzeng Wang, Yining Tao, Zhen Li, Xin He, Huanliang Meng, Hongsheng Wang, Jiakang Shen and 18 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing 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

25 citing papers in PubMed.

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  19. A review of immunotherapy for bone tumors.Frontiers in immunology · 2025
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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

28 authors.

Haoran MuDepartment of Orthopedic Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China.
Qi ZhangDepartment of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Dongqing ZuoDepartment of Orthopedic Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China.
Jinzeng WangNational Research Center for Translational Medicine at Shanghai, State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: jz.wang@sjtu.edu.cn.
Yining TaoDepartment of Orthopedic Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China.
Zhen LiState Key Laboratory of Neurology and Oncology Drug Development, Nanjing, China; Simcere Zaiming Pharmaceutical Co., Ltd., Shanghai, China.
Xin HeDepartment of Orthopedic Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China.
Huanliang MengDepartment of Orthopedic Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China.
Hongsheng WangDepartment of Orthopedic Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China.
Jiakang ShenDepartment of Orthopedic Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China.
Mengxiong SunDepartment of Orthopedic Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China.
Yafei JiangDepartment of Orthopedic Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China.
Weisong ZhaoDepartment of Orthopedic Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China.
Jing HanDepartment of Orthopedic Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China.
Mengkai YangDepartment of Orthopedic Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China.
Zhuoying WangDepartment of Orthopedic Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China.
Yu LvDepartment of Orthopedic Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China.
Yuqin YangDepartment of Laboratory Animal Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jing XuDepartment of Orthopedic Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China.
Tao ZhangDepartment of Orthopedic Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China.
Liu YangDepartment of Orthopedic Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China.
Jun LinDepartment of Pathology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Feng TangState Key Laboratory of Neurology and Oncology Drug Development, Nanjing, China; Jiangsu Simcere Pharmaceutical Co., Ltd., Nanjing, China.
Renhong TangState Key Laboratory of Neurology and Oncology Drug Development, Nanjing, China; Jiangsu Simcere Pharmaceutical Co., Ltd., Nanjing, China; Simcere Zaiming Pharmaceutical Co., Ltd., Shanghai, China.
Haiyan HuThe Drug and Device Phase I Clinical Research Ward/Demonstration Research Ward of Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhengdong CaiDepartment of Orthopedic Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China.
Wei SunDepartment of Orthopedic Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China. Electronic address: viv-sun@sjtu.edu.cn.
Yingqi HuaDepartment of Orthopedic Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China. Electronic address: hua_yingqi@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Osteosarcoma (OS), a malignant bone tumor with limited treatment options, exhibits low sensitivity to immune checkpoint therapy (ICT). Through genomics and transcriptomics analyses, we identify a subgroup of OS with methylthioadenosine phosphorylase (MTAP) deletion, which contributes to ICT resistance, leading to a "cold" tumor microenvironment. MTAP-deleted OS relies on methionine metabolism and is sensitive to methionine intervention, achieved through either dietary restriction or inhibition of methionine adenosyltransferase 2a (MAT2A), a key enzyme in methionine metabolism. We further demonstrate that methionine intervention triggers programmed death-ligand 1 (PD-L1) transcription factor IKAROS family zinc finger 1 (IKZF1) and enhances PD-L1 expression in MTAP-deleted OS cells. Methionine intervention also activates the immune-related signaling pathways in MTAP-deleted OS cells and attracts CD8

Indexed as

B7-H1 AntigenBone NeoplasmsImmune Checkpoint InhibitorsMethionineOsteosarcomaPurine-Nucleoside PhosphorylaseAnimalsCD8-Positive T-LymphocytesCell Line, TumorGene Expression Regulation, NeoplasticHumansMethionine AdenosyltransferaseMiceMice, Inbred C57BLTumor Microenvironment5'-methylthioadenosine phosphorylaseB7-H1 AntigenCD274 protein, humanImmune Checkpoint InhibitorsMethionineMethionine AdenosyltransferasePurine-Nucleoside PhosphorylaseIKZF1immunotherapyMAT2Amethionine metabolismMTAP deletionosteosarcomaPD-L1tumor microenvironment

Identifiers

PMID39983717
PMCPMC11970323

What OpenQuestion holds

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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.