| First Author | Mahadevan KK | Year | 2024 |
| Journal | Science | Volume | 384 |
| Issue | 6703 | Pages | eadh4567 |
| PubMed ID | 38935717 | Mgi Jnum | J:352250 |
| Mgi Id | MGI:7705599 | Doi | 10.1126/science.adh4567 |
| Citation | Mahadevan KK, et al. (2024) Type I conventional dendritic cells facilitate immunotherapy in pancreatic cancer. Science 384(6703):eadh4567 |
| abstractText | 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. |
