BioProject

The addition of immune checkpoint blockade (ICB) to platinum/etoposide chemotherapy changed the standard of care for small cell lung cancer (SCLC) treatment. More...

The addition of immune checkpoint blockade (ICB) to platinum/etoposide chemotherapy changed the standard of care for small cell lung cancer (SCLC) treatment. However, ICB addition only modestly improved clinical outcomes, likely reflecting the high prevalence of an immunologically “cold” tumor microenvironment in SCLC, despite high mutational burden. Nevertheless, some patients clearly benefit from ICB and recent reports have associated clinical responses to ICB in SCLC with A) decreased neuroendocrine characteristics and B) activation of NOTCH signaling. We previously showed that inhibition of the LSD1 demethylase activates NOTCH and suppresses neuroendocrine features of SCLC, leading us to investigate whether LSD1 inhibition would enhance the response to PD1 inhibition in SCLC. Overall design: Identification of differentially expressed genes regulated by exposure to the LSD1 inhibitor bomedemstat (BOM) in cultured murine SCLC cells and an immunocompetent murine flank tumor model of SCLC. Cultured cells were treated with BOM for 96h, or with BOM or control for 10d with or without IFNg for the last 48h. Flank tumors were exposed to BOM or vehicle, with or without anti-PD1 immune checkpoint inhibitor (ICI) antibody, for 16-17 days. Less...