Epigenomic analyses identify FOXM1 as a key regulator of anti-tumor immune response in esophageal adenocarcinoma.
Cell Death Dis
; 15(2): 152, 2024 Feb 19.
Article
in En
| MEDLINE
| ID: mdl-38373993
ABSTRACT
Unlike most cancer types, the incidence of esophageal adenocarcinoma (EAC) has rapidly escalated in the western world over recent decades. Using whole genome bisulfite sequencing (WGBS), we identify the transcription factor (TF) FOXM1 as an important epigenetic regulator of EAC. FOXM1 plays a critical role in cellular proliferation and tumor growth in EAC patient-derived organoids and cell line models. We identify ERBB2 as an upstream regulator of the expression and transcriptional activity of FOXM1. Unexpectedly, gene set enrichment analysis (GSEA) unbiased screen reveals a prominent anti-correlation between FOXM1 and immune response pathways. Indeed, syngeneic mouse models show that FOXM1 inhibits the infiltration of CD8+ T cells into the tumor microenvironment. Consistently, FOXM1 suppresses CD8+ T cell chemotaxis in vitro and antigen-dependent CD8+ T cell killing. This study characterizes FOXM1 as a significant EAC-promoting TF and elucidates its novel function in regulating anti-tumor immune response.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Esophageal Neoplasms
/
Adenocarcinoma
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CD8-Positive T-Lymphocytes
/
Forkhead Box Protein M1
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Death Dis
Year:
2024
Document type:
Article
Affiliation country: