Proteasome-dependent senescent tumor cells mediate immunosuppression through CCL20 secretion and M2 polarization in pancreatic ductal adenocarcinoma.

ABSTRACT: The outcome of pancreatic ductal adenocarcinoma (PDAC) remains poor due to few therapeutic options available and challenges with precision therapy to target each tumour's specific characteristics. In this study, a biologically meaningful patient stratification-prognostic model with therapeutic suggestion value based on tumor senescence was developed and validated in multiple independent cohorts. Further mechanistic investigation based on single-cell transcriptomic data and in vitro experiments revealed that complement derived from non-senescent tumor cells stimulates M1 differentiation and antigen presentation, while senescent tumor cells secrete CCL20 to favor immunosuppressive M2 polarization. Also, senescent phenotype depends on proteasome function, suggesting that high-risk, hig

SUBMITTER: Wu M 

PROVIDER: S-EPMC10310997 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature