CREBBP loss drives immune evasion by epigenetically silencing STING and MHC-I in small cell lung cancer.

CREBBP loss is linked to immune evasion and immunotherapy resistance in small cell lung cancer by silencing STING and MHC-I expression.

• Why it matters: Understanding the mechanisms behind low immunogenicity and resistance to immunotherapy in SCLC is crucial for developing effective treatments.
• What they did: Researchers used Rb1/Trp53-driven mouse models and syngeneic SCLC models to show that CREBBP deletion suppresses STING and MHC-I by reducing histone H3 acetylation, and that HDAC inhibition can restore gene expression and immune responses.
• The result: HDAC inhibitors combined with immune checkpoint blockade more effectively suppressed tumor growth, especially in CREBBP-mutant tumors, suggesting HDAC inhibition may improve immunotherapy outcomes in SCLC.