Evidence map›Paper›PMID 39744942›Full record

ArticleThe Journal of clinical investigation2025

T helper 2 cell-directed immunotherapy eliminates precancerous skin lesions.

Tomonori Oka, Sabrina S Smith, Heehwa G Son, Truelian Lee, Valeria S Oliver-Garcia, Mahsa Mortaja, Kathryn E Trerice, Lily S Isakoff, Danielle N Conrad, Marjan Azin and 7 more

Abstract read
In one paragraph

Article in The Journal of clinical investigation, 2025. 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. 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

17 authors.

Tomonori OkaCenter for Cancer Immunology and Cutaneous Biology Research Center, Krantz Family Center for Cancer Research and Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Sabrina S SmithCenter for Cancer Immunology and Cutaneous Biology Research Center, Krantz Family Center for Cancer Research and Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Heehwa G SonCenter for Cancer Immunology and Cutaneous Biology Research Center, Krantz Family Center for Cancer Research and Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Truelian LeeCenter for Cancer Immunology and Cutaneous Biology Research Center, Krantz Family Center for Cancer Research and Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Valeria S Oliver-GarciaCenter for Cancer Immunology and Cutaneous Biology Research Center, Krantz Family Center for Cancer Research and Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Mahsa MortajaCenter for Cancer Immunology and Cutaneous Biology Research Center, Krantz Family Center for Cancer Research and Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Kathryn E TrericeCenter for Cancer Immunology and Cutaneous Biology Research Center, Krantz Family Center for Cancer Research and Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Lily S IsakoffCenter for Cancer Immunology and Cutaneous Biology Research Center, Krantz Family Center for Cancer Research and Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Danielle N ConradCenter for Cancer Immunology and Cutaneous Biology Research Center, Krantz Family Center for Cancer Research and Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Marjan AzinCenter for Cancer Immunology and Cutaneous Biology Research Center, Krantz Family Center for Cancer Research and Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Neel S RavalDivision of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Mary TabacchiDivision of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Luni EmdadDepartment of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA.
Swadesh K DasDepartment of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA.
Paul B FisherDepartment of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA.
Lynn A CorneliusDivision of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Shadmehr DemehriCenter for Cancer Immunology and Cutaneous Biology Research Center, Krantz Family Center for Cancer Research and Department of Dermatology, Massachusetts General Hospital, Boston, Massachusetts, USA.

Funding

Virus Vector Shared ResourceP30CA016059 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Renato Martins · 1985 to 2026
$51.0M
Mouse Model and Pathological Analysis CoreP01CA275740 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Nolan Wages · 2024 to 2026
$10.6M
DERMATOLOGY TRAINING GRANTT32AR007098 · NIAMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI THOMAS S. KUPPER · 1986 to 2026
$8.1M
Interplay between tumor and microenvironment in bone metastasisR01CA259599 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI FISHER, PAUL B, WANG, XIANG-YANG SHAWN · 2021 to 2025
$2.3M
Immunotherapy for Skin Cancer Precursors to Prevent Skin CancerR01AR076013 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI DEMEHRI, SHADMEHR · 2019 to 2023
$1.8M
NCI NIH HHS P01 CA275740NCI NIH HHS P30 CA016059NCI NIH HHS R01 CA259599NIAMS NIH HHS R01 AR076013NIAMS NIH HHS T32 AR007098
6 · The paper itself

Abstract

The continuous rise in skin cancer incidence highlights an imperative for improved skin cancer prevention. Topical calcipotriol-plus-5-fluorouracil (calcipotriol-plus-5-FU) immunotherapy effectively eliminates precancerous skin lesions and prevents squamous cell carcinoma (SCC) in patients. However, its mechanism of action remains unclear. Herein, we demonstrate that calcipotriol-plus-5-FU immunotherapy induces T helper type 2 (Th2) immunity, eliminating premalignant keratinocytes in humans. CD4+ Th2 cells were required and were sufficient downstream of thymic stromal lymphopoietin cytokine induction by calcipotriol to suppress skin cancer development. Th2-associated cytokines induced IL-24 expression in cancer cells, resulting in toxic autophagy and anoikis followed by apoptosis. Calcipotriol-plus-5-FU immunotherapy was dependent on IL-24 to suppress skin carcinogenesis in vivo. Collectively, our findings establish a critical role for Th2 immunity in cancer immunoprevention and highlight the Th2/IL-24 axis as an innovative target for skin cancer prevention and therapy.

Indexed as

CalcitriolFluorouracilInterleukinsPrecancerous ConditionsSkin NeoplasmsTh2 CellsAnimalsCarcinoma, Squamous CellCytokinesHumansImmunotherapyInterleukin-24KeratinocytesMicecalcipotrieneCalcitriolCytokinesFluorouracilInterleukin-24InterleukinsDermatologyImmunotherapyOncologySkin cancerT cells

Identifiers

PMID39744942
PMCPMC11684800

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.