Evidence map›Paper›PMID 40595560›Full record

ArticleNature communications2025

Exploitable mechanisms of antibody and CAR mediated macrophage cytotoxicity.

Tianyi Liu, Meng Zhang, Tatyanah Farsh, Haolong Li, Audrey Kishishita, Abhilash Barpanda, Stanley G Leung, Jun Zhu, Hyuncheol Jung, Junjie Tony Hua and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Article
  5. CAR-macrophages: a new chapter in cancer immunotherapy.Acta biochimica et biophysica Sinica · 2026
    Article
  6. Targeting Macrophages in Immunotherapy: The Ascent of CAR-Macrophages.International journal of molecular sciences · 2026
    Review
  7. Activation of FCGR2A enhances the antitumor efficacy of hPSC-derived CAR-M.Frontiers in cell and developmental biology · 2025
    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

27 authors.

Tianyi LiuUniversity of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 94158, USA.
Meng ZhangUniversity of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0003-1042-6294
Tatyanah FarshUniversity of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0009-0000-8058-1033
Haolong LiUniversity of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0002-8628-9698
Audrey KishishitaDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Abhilash BarpandaDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, 94158, USA.
Stanley G LeungUniversity of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 94158, USA.
Jun ZhuUniversity of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 94158, USA.
Hyuncheol JungGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, 94158, USA.
Junjie Tony HuaUniversity of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 94158, USA.
Xiaolin ZhuUniversity of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0002-3221-595X
Alexander B KimDepartment of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, 63108, USA.ORCID http://orcid.org/0000-0002-6425-4566
Young Ah GooMass Spectrometry Technology Access Center at McDonnell Genome Institute (MTAC@MGI) at Washington University School of Medicine, St. Louis, MO, 63108, USA.
Minsoo SonMass Spectrometry Technology Access Center at McDonnell Genome Institute (MTAC@MGI) at Washington University School of Medicine, St. Louis, MO, 63108, USA.ORCID http://orcid.org/0000-0001-8531-0320
Jaenyeon KimMass Spectrometry Technology Access Center at McDonnell Genome Institute (MTAC@MGI) at Washington University School of Medicine, St. Louis, MO, 63108, USA.ORCID http://orcid.org/0009-0006-2836-0392
Aish SubramanianUniversity of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 94158, USA.
Martin SjöströmDepartment of Radiation Oncology, University of California, San Francisco, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0002-2629-9966
Katherine C FuhUniversity of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0002-7693-2694
Jocelyn S ChapmanUniversity of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0002-4260-3016
Julia CarnevaleUniversity of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0001-9410-7148
Luke A GilbertUniversity of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0001-5854-0825
Aparna LakkarajuPharmaceutical Sciences and Pharmacogenomics, University of California San Francisco, San Francisco, CA, 94143, USA.
Peter M BrunoUniversity of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0003-3383-0118
David QuigleyUniversity of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0002-4726-1473
Arun P WiitaDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0002-7465-6964
Felix Y FengUniversity of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 94158, USA.ORCID http://orcid.org/0000-0002-0963-7687
Carl J DeSelmDepartment of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, 63108, USA. deselmc@wustl.edu.ORCID http://orcid.org/0000-0001-7645-5798

Funding

Immune Activating CAR-Modified Antigen Presenting CellsDP5OD026427 · OD · WASHINGTON UNIVERSITY · PI DESELM, CARL · 2018 to 2022
$2.0M
NIH HHS DP5 OD026427U.S. Department of Health & Human Services | National Institutes of Health (NIH) DP5OD026427
6 · The paper itself

Abstract

Macrophages infiltrate solid tumors and either support survival or induce cancer cell death through phagocytosis or cytotoxicity. To uncover regulators of macrophage cytotoxicity towards cancer cells, we perform two co-culture CRISPR screens using CAR-macrophages targeting different tumor associated antigens. Both identify ATG9A as an important regulator of this cytotoxic activity. In vitro and in vivo, ATG9A depletion in cancer cells sensitizes them to macrophage-mediated killing. Proteomic and lipidomic analyses reveal that ATG9A deficiency impairs the cancer cell response to macrophage-induced plasma membrane damage through defective lysosomal exocytosis, reduced ceramide production, and disrupted caveolar endocytosis. Depleting non-cytotoxic macrophages using CSF1R inhibition while preventing ATG9A-mediated tumor membrane repair enhances the anti-tumor activity of therapeutic antibodies in mice. Thus, macrophage cytotoxicity plays an important role in tumor elimination during antibody or CAR-macrophage treatment, and inhibiting tumor membrane repair via ATG9A, particularly in combination with cytotoxic macrophage enrichment through CSF1R inhibition, improves tumor-targeting macrophage efficacy.

Indexed as

MacrophagesNeoplasmsReceptors, Chimeric AntigenAnimalsAntigens, NeoplasmAutophagy-Related ProteinsCell Line, TumorCell MembraneCoculture TechniquesExocytosisFemaleHumansLysosomesMembrane ProteinsMicePhagocytosisAntigens, NeoplasmAutophagy-Related ProteinsCsf1r protein, mouseMembrane ProteinsReceptors, Chimeric AntigenReceptors, Granulocyte-Macrophage Colony-Stimulating FactorVesicular Transport Proteins

Identifiers

PMID40595560
PMCPMC12216399

What OpenQuestion 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 OpenQuestion graph.