TY - JOUR
T1 - Type I conventional dendritic cells facilitate immunotherapy in pancreatic cancer
AU - Mahadevan, Krishnan K.
AU - Dyevoich, Allison M.
AU - Chen, Yang
AU - Li, Bingrui
AU - Sugimoto, Hikaru
AU - Sockwell, Amari M.
AU - McAndrews, Kathleen M.
AU - Sthanam, Lakshmi Kavitha
AU - Wang, Huamin
AU - Shalapour, Shabnam
AU - Watowich, Stephanie S.
AU - Kalluri, Raghu
PY - 2024/6/28
Y1 - 2024/6/28
N2 - 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.
AB - 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.
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U2 - 10.1126/science.adh4567
DO - 10.1126/science.adh4567
M3 - Article
C2 - 38935717
AN - SCOPUS:85197203301
SN - 0036-8075
VL - 384
SP - eadh4567
JO - Science (New York, N.Y.)
JF - Science (New York, N.Y.)
IS - 6703
ER -