125P LSD1 inhibition restores MHC class I expression and augments the anti-tumor response of immune checkpoint blockade in small cell lung cancer

Abstract

Small cell lung cancer (SCLC) is a poorly immunogenic, high-grade neuroendocrine carcinoma. SCLC is largely unresponsive to immune checkpoint blockade (ICB) due to immunosuppressive mechanisms like repression of the major histocompatibility complex class I (MHC-I) and lack of T cell infiltration. Chromatin regulator, histone H3K4 demethylase LSD1 (gene KDM1A), is highly expressed in SCLC cells and has been shown to have immunosuppressive effects in other cancers. However, how LSD1 modulates the immune microenvironment and tumor responses to cancer immunotherapy in SCLC is still poorly understood.