Combined Autophagy Inhibition and Dendritic Cell Recruitment Induces Antitumor Immunity and Enhances Immune Checkpoint Blockade Sensitivity in Pancreatic Cancer.

ABSTRACT: The effect of immune checkpoint inhibitors is extremely limited in patients with pancreatic ductal adenocarcinoma (PDAC) due to the suppressive tumor immune microenvironment. Autophagy, which has been shown to play a role in antitumor immunity, has been proposed as a therapeutic target for PDAC. In this study, single-cell RNA sequencing of autophagy-deficient murine PDAC tumors revealed that autophagy inhibition in cancer cells induced dendritic cell (DC) activation. Analysis of human PDAC tumors substantiated a negative correlation between autophagy and DC activation signatures. Mechanistically, autophagy inhibition increased the intracellular accumulation of tumor antigens, which could activate DCs. Administration of chloroquine, an autophagy inhibitor, in combination with Flt3 ligand-in

SUBMITTER: Oyama K 

PROVIDER: S-EPMC11647207 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature