Evidence map›Paper›PMID 40250424›Full record

ArticleCell reports2025

Epigenomic regulation of stemness contributes to the low immunogenicity of the most mutated human cancer.

Tomonori Oka, Sabrina S Smith, Valeria S Oliver-Garcia, Truelian Lee, Heehwa G Son, Mahsa Mortaja, Marjan Azin, Anna C Garza-Mayers, Jennifer T Huang, Rosalynn M Nazarian and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. 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. An immunocompetent transplantable mouse model of basal cell carcinoma.JID innovations : skin science from molecules to population health · 2026
    Article
  2. Review
  3. Review
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

12 authors.

Tomonori OkaCenter for Cancer Immunology and Cutaneous Biology Research Center, Department of Dermatology and Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Sabrina S SmithCenter for Cancer Immunology and Cutaneous Biology Research Center, Department of Dermatology and Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Valeria S Oliver-GarciaCenter for Cancer Immunology and Cutaneous Biology Research Center, Department of Dermatology and Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Truelian LeeCenter for Cancer Immunology and Cutaneous Biology Research Center, Department of Dermatology and Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Heehwa G SonCenter for Cancer Immunology and Cutaneous Biology Research Center, Department of Dermatology and Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Mahsa MortajaCenter for Cancer Immunology and Cutaneous Biology Research Center, Department of Dermatology and Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Marjan AzinCenter for Cancer Immunology and Cutaneous Biology Research Center, Department of Dermatology and Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Anna C Garza-MayersDepartment of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Jennifer T HuangDermatology Section, Division of Immunology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Rosalynn M NazarianDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Thomas D HornDepartment of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Shadmehr DemehriCenter for Cancer Immunology and Cutaneous Biology Research Center, Department of Dermatology and Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: sdemehri1@mgh.harvard.edu.

Funding

Immunotherapy for Skin Cancer Precursors to Prevent Skin CancerR01AR076013 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI DEMEHRI, SHADMEHR · 2019 to 2023
$1.8M
NIAMS NIH HHS R01 AR076013
6 · The paper itself

Abstract

Despite harboring the highest tumor mutational burden of all cancers, basal cell carcinoma (BCC) has low immunogenicity. Here, we demonstrate that BCC's low immunogenicity is associated with epigenomic suppression of antigen presentation machinery reminiscent of its cell of origin. Primary BCC had low T cell infiltrates and low human leukocyte antigen class I (HLA-I) expression compared with cutaneous squamous cell carcinoma (SCC) and normal keratinocytes. Forkhead box C1 (Foxc1), a regulator of quiescence in hair follicle stem cells, was expressed in BCC. Foxc1 bound to promoter of interferon regulatory factor 1 and HLA-I genes, leading to their deacetylation and reduced expression. A histone deacetylase inhibitor, entinostat, overcame Foxc1's effect and upregulated HLA-I in BCC. Topical entinostat plus imiquimod immunotherapy blocked BCC development in mice. Collectively, our findings demonstrate that low BCC immunogenicity is associated with a stem-like quiescent program preserved in the tumor cells, which can be blocked to enable BCC immunotherapy.

Indexed as

Basal Cell CarcinomaEpigenesis, GeneticEpigenomicsMutationNeoplastic Stem CellsSkin NeoplasmsAnimalsBenzamidesCarcinoma, Squamous CellCell Line, TumorForkhead Transcription FactorsGene Expression Regulation, NeoplasticHistocompatibility Antigens Class IHumansImiquimodImmunotherapyBenzamidesentinostatForkhead Transcription FactorsHistocompatibility Antigens Class IImiquimodPyridinesantigen processing and presentation machinerybasal cell carcinomaCP: Cancercutaneous squamous cell carcinomaentinostatFoxc1hair follicle stem cellHLA-IimmunotherapyIRF1

Identifiers

PMID40250424
PMCPMC12149994

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.