Bcl-xL blockade targets neutrophils and synergizes with chemotherapy in lung squamous cell carcinoma

ABSTRACT: Tumor-associated neutrophils (TANs) represent a large fraction of immune cells in tumors, but how their regulation and function vary in distinct cancer subtypes remains unknown. In KrasLSL-G12D/WT; p53fl/fl mouse models of lung adenocarcinoma (LUAD), TANs have an increased lifespan compared to normal neutrophils. Specifically, TANs upregulate the anti-apoptotic protein Bcl-xL, whose blockade by a BH3 mimetic selectively kills ageing TANs and diminishes tumor growth. Here, we have addressed this issue in lung squamous cell carcinoma (LUSC) using the Rosa26LSL-Sox2-IRES-GFP; Nkx2-1fl/fl; Lkb1fl/fl mouse model, where we demonstrate increased TAN survival with a rise in Bcl-xL similarly to LUAD. However, unlike in LUAD, inhibiting Bcl-xL alone was insufficient to alter tumor progression in LUS

SUBMITTER: Abdullah Mayet 

PROVIDER: S-SCDT-10_1038-S44321-026-00401-Z | biostudies-other |

REPOSITORIES: biostudies-other