Evidence map›Paper›PMID 41968179›Full record

ArticleSignal transduction and targeted therapy2026

Bioengineered iPSC-derived human macrophages with increased angiotensin-converting enzyme (ACE) expression suppress solid tumor growth.

Tomohiro Shibata, Shabir Bhat, DuoYao Cao, Suguru Saito, Noor Khan, Ellen A Bernstein, Takeshi Tokudome, Derick Okwan-Duodu, Warren G Tourtellotte, Kenneth E Bernstein and 1 more

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Article in Signal transduction and targeted therapy, 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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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

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

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4 · The record

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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

11 authors.

Tomohiro ShibataDepartment of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Shabir BhatDepartment of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
DuoYao CaoDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Suguru SaitoDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Noor KhanDepartment of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Ellen A BernsteinDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Takeshi TokudomeDepartment of Pharmacology, Yokohama City University School of Medicine, Yokohama, Japan.
Derick Okwan-DuoduDepartment of Pathology, Stanford University, Stanford, CA, USA.
Warren G TourtellotteDepartment of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Kenneth E BernsteinDepartment of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Zakir KhanDepartment of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. zkhan@imbcr.org.

Funding

Cedars-Sinai Medical Center (Cedars-Sinai) 229154Cedars-Sinai Medical Center (Cedars-Sinai) 233040
6 · The paper itself

Abstract

The potential of the immune system to decrease cancer progression is widely recognized and has led to the development of innovative anti-cancer immunotherapies. Here, we studied human macrophages derived from genetically engineered iPSCs (iMac) with angiotensin-converting enzyme (ACE) expression regulatable by a doxycycline (dox)-inducible promoter as a novel anti-cancer immunotherapy. Increased ACE expression in iMac (cells now termed ACE-iMac) augments polarization towards an M1 macrophage phenotype characterized by increased production of proinflammatory cytokines, reactive oxygen species, nitric oxide, and an RNA profile indicating an aggressive immune response. ACE-iMac kills tumor cells in vitro significantly better than iMac. In vivo, studies using tumor xenografts for melanoma, breast cancer, and head and neck squamous cell carcinoma (HNSCC) showed a highly significant 3.4- to 7.2-fold reduction in solid tumor size following ACE-expressing ACE-iMac immunotherapy as compared to results with iMac. To further investigate the impact of ACE on human anti-tumor responses, we developed a humanized BLT-NSG mouse model with a fully functional adaptive immune system. Here, ACE-iMac treatment significantly reduced the growth of human melanoma xenografts by enhancing the activation of human T cells and NK cells. In conclusion, enhancing ACE expression in human-derived macrophages (ACE-iMac) greatly amplifies their anti-cancer phenotype, offering a compelling new therapeutic strategy with the potential to improve clinical outcomes for cancer patients.

Indexed as

Induced Pluripotent Stem CellsMacrophagesMelanomaPeptidyl-Dipeptidase AAnimalsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansImmunotherapyMiceXenograft Model Antitumor AssaysPeptidyl-Dipeptidase A

Identifiers

PMID41968179
PMCPMC13071079

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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.