Evidence map›Paper›PMID 41491403›Full record

ArticleNature immunology2026

Targeting autocrine retinoic acid signaling by ALDH1A2 inhibition enhances antitumor dendritic cell vaccine efficacy.

Cao Fang, Mark Esposito, Ulrike Hars, Robert T Byrne, Bokai Song, Jian Huang, Asael Roichman, Lawrence Shue, Xiaobing Cheng, John Proudfoot and 5 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. 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

15 authors.

Cao FangDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0000-0002-5001-3323
Mark EspositoDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0000-0002-5724-4087
Ulrike HarsCrelux, a WuXi AppTec company, Gräfelfing, Germany.
Robert T ByrneCrelux, a WuXi AppTec company, Gräfelfing, Germany.
Bokai SongDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.
Jian HuangDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0000-0002-6861-0425
Asael RoichmanDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.
Lawrence ShueDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0000-0003-4525-9270
Xiaobing ChengResearch Chemistry Services, WuXi AppTec, Tianjin, China.
John ProudfootDiscoveryBytes, Newtown, CT, USA.
Demin ZhaoDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.
Yong WeiDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0000-0002-1034-649X
Ileana M CristeaDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0000-0002-6533-2458
Joshua D RabinowitzDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.ORCID http://orcid.org/0000-0002-1247-4727
Yibin KangDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA. ykang@princeton.edu.ORCID http://orcid.org/0000-0002-1626-6730

Funding

Ludwig Institute for Cancer Research (Ludwig Cancer Research) N/ASusan G. Komen (Susan G. Komen Breast Cancer Foundation) SAC220223
6 · The paper itself

Abstract

Strategies to stimulate dendritic cell (DC) activity, such as ex vivo generation and priming of DC vaccines, have been explored as cancer immunotherapies owing to their potential to elicit antitumor T cell responses. Despite decades of research, the success of DC vaccines has been limited, potentially because of unidentified tolerance-enforcing mechanisms. Here we show that GM-CSF-IL-4-induced differentiating DCs express ALDH1A2 and produce retinoic acid, inhibiting DC maturation. Genetic knockout of Aldh1a2 releases this natural brake and enhances DC function. We further develop an ALDH1A2 inhibitor with high potency, favorable drug-like properties and no evidence of off-target effects. Treatment with this inhibitor promotes DC activity, which in turn enhances antigen-specific T cell responses, improving the efficacy of DC vaccines. Our study demonstrates the unique role of the ALDH1A2-retinoic acid axis in regulating DC functions and further presents a new small-molecule inhibitor of ALDH1A2 as a potential immunotherapeutic agent for cancer.

Indexed as

Cancer VaccinesDendritic CellsRetinal DehydrogenaseTretinoinAldehyde Dehydrogenase 1 FamilyAnimalsCell DifferentiationFemaleGranulocyte-Macrophage Colony-Stimulating FactorHumansImmunotherapyMiceMice, Inbred C57BLMice, KnockoutSignal TransductionAldehyde Dehydrogenase 1 FamilyALDH1A2 protein, humanAldh1a2 protein, mouseCancer VaccinesGranulocyte-Macrophage Colony-Stimulating FactorRetinal DehydrogenaseTretinoin

Identifiers

PMID41491403

What OpenQuestion holds

Textmetadata
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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.