%0 Journal Article
%T Type I conventional dendritic cells facilitate immunotherapy in pancreatic cancer.
%A Mahadevan KK
%A Dyevoich AM
%A Chen Y
%A Li B
%A Sugimoto H
%A Sockwell AM
%A McAndrews KM
%A Sthanam LK
%A Wang H
%A Shalapour S
%A Watowich SS
%A Kalluri R
%J Science
%V 384
%N 6703
%D 2024 Jun 28
%M 38935717
%F 63.714
%R 10.1126/science.adh4567
%X Inflammation and tissue damage associated with pancreatitis can precede or occur concurrently with pancreatic ductal adenocarcinoma (PDAC). We demonstrate that in PDAC coupled with pancreatitis (ptPDAC), antigen-presenting type I conventional dendritic cells (cDC1s) are specifically activated. Immune checkpoint blockade therapy (iCBT) leads to cytotoxic CD8+ T cell activation and elimination of ptPDAC with restoration of life span even upon PDAC rechallenge. Using PDAC antigen-loaded cDC1s as a vaccine, immunotherapy-resistant PDAC was rendered sensitive to iCBT with elimination of tumors. cDC1 vaccination coupled with iCBT identified specific CDR3 sequences in the tumor-infiltrating CD8+ T cells with potential therapeutic importance. This study identifies a fundamental difference in the immune microenvironment in PDAC concurrent with, or without, pancreatitis and provides a rationale for combining cDC1 vaccination with iCBT as a potential treatment option.