Single-cell RNA sequencing reveals compartmental remodeling of tumor-infiltrating immune cells induced by anti-CD47 targeting in pancreatic cancer.

ABSTRACT: BACKGROUND:Human pancreatic ductal adenocarcinoma (PDAC) responds poorly to immune checkpoint inhibitor (ICPi). While the mechanism is not completely clear, it has been recognized that tumor microenvironment (TME) plays key roles. We investigated if targeting CD47 with a monoclonal antibody could enhance the response of PDAC to ICPi by altering the TME. METHODS:Using immunohistochemistry, we examined tumor-infiltrating CD68+ pan-macrophages (CD68+ M) and CD163+ M2 macrophages (CD163+ M2) and tumor expression of CD47 and PD-L1 proteins in 106 cases of PDAC. The efficacy of CD47 blockade was examined in xenograft models. CD45+ immune cells from syngeneic tumor models were subjected to single-cell RNA-sequencing (scRNA-seq) by using the 10x Genomics pipeline. RESULTS:We found that CD47 expres

SUBMITTER: Pan Y 

PROVIDER: S-EPMC6880569 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature