{Reference Type}: Journal Article
{Title}: Type I conventional dendritic cells facilitate immunotherapy in pancreatic cancer.
{Author}: Mahadevan KK;Dyevoich AM;Chen Y;Li B;Sugimoto H;Sockwell AM;McAndrews KM;Sthanam LK;Wang H;Shalapour S;Watowich SS;Kalluri R;
{Journal}: Science
{Volume}: 384
{Issue}: 6703
{Year}: 2024 Jun 28
{Factor}: 63.714
{DOI}: 10.1126/science.adh4567
{Abstract}: 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.