7MO WEE1 inhibition enhances the antitumor immune response to PD-L1 blockade by the concomitant activation of STING and STAT1 pathways in small cell lung cancer

Abstract

Small cell lung cancer (SCLC) is a poorly immunogenic, high-grade neuroendocrine carcinoma arising in the lung. Immune checkpoint blockade (ICB) added to chemotherapy is now the standard upfront therapy for SCLC but leads to a modest increase in overall survival and progression-free survival. These modest benefits underscore the critical need to identify pathways and targets that can durably enhance the antitumor responses of ICB in SCLC. SCLC is characterized by a ubiquitous loss of TP53 which disrupts the G1-S cell cycle checkpoint and as a result, most SCLC is dependent on G2-M cell cycle checkpoint regulators including WEE1.