Evidence map›Paper›PMID 42574617›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2026

Single-cell multiomics identifies an ALDH9A1-carnitine signaling axis driving resistance of NSCLC to immunotherapy.

Hailei Du, Tong Lang, Xiaoxue Zha, Chao Qu, Ling Chen, Shihua Yao, Xing Feng, Zhaohui Jin

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 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. Single-cell multiomics identifies an ALDH9A1-carnitine signaling axis driving resistance of NSCLC to immunotherapy.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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

8 authors.

Hailei Du *Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.ORCID 0000-0002-6126-3176
Tong Lang *Department of Respiratory and Critical Care Medicine, Weifang Second People's Hospital, Weifang 261041, Shandong, China.ORCID 0009-0006-7165-3465
Xiaoxue Zha *Department of Intensive Care Medicine, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230031, Anhui, China.ORCID 0009-0004-6145-5137
Chao QuDepartment of Interventional Therapy, The First Hospital of Jilin University, Changchun 130012, Jilin, China.ORCID 0000-0001-5226-1139
Ling ChenDepartment of Respiratory and Critical Care Medicine Ruijin Hospital, North, Shanghai Jiaotong University School of Medicine, Shanghai 201821, China.ORCID 0000-0002-0150-4433
Shihua YaoDepartment of Thoracic Surgery, Navy Military Medical University Affiliated Changhai Hospital, Shanghai 200433, China.ORCID 0009-0007-7032-0893
Xing FengDepartment of Immunobiology and Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT 06510.ORCID 0000-0002-2253-4180
Zhaohui JinDepartment of Pharmacy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.ORCID 0009-0009-0660-1695

Funding

National Natural Science Foundation of China 82070256National Natural Science Foundation of China 82073373
6 · The paper itself

Abstract

Immunotherapy resistance remains a major barrier to achieving sustained patient improvement in non-small cell lung cancer (NSCLCs). Here, through integrating CODEX, metabolomics, CyTOF, ATAC-seq, and single-cell spatial transcriptomics from NSCLC tumors, we uncover an unrecognized role of ALDH9A1 in promoting resistance to anti-PD-1 therapy. In immunocompetent, but not immunocompromised mouse models, loss of ALDH9A1 markedly restrains tumor growth. This effect is accompanied by increased maturation of tertiary lymphoid structures and reduced accumulation of protumorigenic MDSCs within tumor immune microenvironment. Mechanistically, ALDH9A1-driven carnitine production elevates acetyl-CoA levels, remodels chromatin accessibility, and activates Il1b superenhancers in tumor cells, thereby promoting MDSC polarization and CD8

Indexed as

Carcinoma, Non-Small-Cell LungCarnitineDrug Resistance, NeoplasmLung NeoplasmsAnimalsCell Line, TumorHumansImmunotherapyInterleukin-1betaMiceMultiomicsSignal TransductionSingle-Cell AnalysisTumor MicroenvironmentCarnitineInterleukin-1betaALDH9A1carnitine metabolismIL-1βMDSCssuperenhancer

Identifiers

PMID42574617
PMCPMC13486599

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.