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HDAC inhibition unlocks tumor plasticity and enhances immunotherapy response in Myc- Driven Small Cell Lung Cancer

GSE309192 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2026/04/02 Platform GPL17021
Summary
Small Cell Lung Cancer (SCLC) is a highly aggressive malignancy, accounting for approximately 15% of all lung cancer cases. Characterized by low immunogenicity, SCLC may utilize epigenetic mechanisms to evade immune detection. Here, we demonstrate that entinostat, a class I histone deacetylase inhibitor (HDACi) upregulates immune-related genes in human SCLC cells. In vivo, we confirmed entinostat treatment increased expression of immunecheckpoint ligands and antigen presentation machinery in Myc-driven tumors in a Rb1/Trp53/MycT58A (RPM) SCLC mouse model, while shifting tumors from a neuroendocrine(NE)-high to a NE-low phenotype. Notably, combining entinostat with anti-PD-1 immunotherapy significantly enhances T-cell infiltration, suppresses tumor growth, and prolongs survival in RPM allograft models. These findings underscore the potential of entinostat to reprogram the immunological landscape and NE status of SCLC, enhance immune checkpoint blockade efficacy, and improve therapeutic outcomes.
Published in
HDAC inhibition unlocks tumor plasticity and enhances immunotherapy response in Myc-driven small cell lung cancer
Ghafoor A, Zhu L, Weaver Ohler Z et al. · Molecular cancer therapeutics 2026 · PMID 42068133 · doi:10.1158/1535-7163.MCT-25-1077
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Also filed as BioProject PRJNA1334306 and SRA study SRP627152. Searching any of these in the dataset finder brings you back here.

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