Evidence map›Paper›PMID 40068101›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

The Nuclear Receptor NR1B1/RARα Arrests the Differentiation of Anti-Tumor Effector Cytotoxic T Cells.

Patrick Niekamp, Ryun Hee Kim, Adithyan Jayaraman, Nils Klement, Raymond Kostlan, Chang H Kim

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

6 authors.

Patrick NiekampDepartment of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA.
Ryun Hee KimDepartment of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA.
Adithyan JayaramanDepartment of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA.
Nils KlementUniversity of Bielefeld, Faculty of Physics, 33615, Bielefeld, Germany.
Raymond KostlanDepartment of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA.
Chang H KimDepartment of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA.ORCID https://orcid.org/0000-0003-4618-9139

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alexey I Nesvizhskii · 1988 to 2026
$178.2M
Transgenic Mouse Core Facility Shared Resource (TMCF-SR)P30CA023168 · NCI · PURDUE UNIVERSITY WEST LAFAYETTE · PI Andrea L Kasinski · 1985 to 2026
$43.4M
Homing of Functionally Distinct ILC SubsetsR01AI121302 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KIM, CHANG H · 2016 to 2020
$1.9M
Mobilization and trafficking of central ILC progenitorsR01AI173179 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHANG H KIM · 2023 to 2026
$1.7M
Regulation of the development of dendritic cells in barrier tissues by retinoid gradientsR21AI148898 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KIM, CHANG H · 2020 to 2021
$414k
Kenneth and Judy Betz Professorship in Food Allergy ResearchNCI NIH HHS P30 CA023168NCI NIH HHS P30 CA046592NIAID NIH HHS R01 AI121302NIAID NIH HHS R01 AI173179NIAID NIH HHS R21 AI148898NIH HHS R01AI121302NIH HHS R01AI173179NIH HHS R21AI148898Rogel Cancer Center, University of Michigan G029699Rogel Cancer Center, University of Michigan P30CA046592
6 · The paper itself

Abstract

NR1B1/RARα expression is dynamically regulated in cytotoxic lymphocytes (CTLs) in tumors, but the importance of its expression in anti-tumor CTLs remains unknown. RARα gene expression is upregulated in CTLs in tumor microenvironments (TME), but its protein expression is downregulated by retinoic acid. The role of RARα expression in regulating anti-tumor effector CTL (Teff) differentiation is reported. Mice that over-express RARα in T cells are defective in early Teff differentiation and fail to populate tumors. In contrast, RARα-deficient CTLs are hyper-active in making tumor-populating Teff cells, suggesting that RARα represses Teff differentiation. Moreover, RARα negatively controls the trafficking receptor switch from the lymphoid to an effector type. Generation of chimeric antigen receptor (CAR) T cells with reduced RARα expression produces highly effective CAR T cells with enhanced anti-tumor cytotoxicity. Mechanistically, upregulated RARα expression decreases the nuclear histone acetylase (HAT) activity, required for TCF1 to BATF transcription factor and trafficking switches during Teff differentiation. Additionally, RARα and BATF closely associate with each other on Teff-associated genes on the chromatin for possible cross-regulation. In sum, T cell-expressed RARα is identified as a novel negative regulator and potential target of intervention in promoting anti-cancer T cell immunity.

Indexed as

Cell DifferentiationRetinoic Acid Receptor alphaT-Lymphocytes, CytotoxicAnimalsHumansMiceMice, Inbred C57BLTumor MicroenvironmentRetinoic Acid Receptor alphaBATFCD8 T cellshistone deacetylaseRARαretinoic acidtrafficking receptor switchtumors

Identifiers

PMID40068101
PMCPMC12061256

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.