研究人员表示，与胰腺炎相关的炎症和组织损伤可在胰腺导管腺癌（PDAC）之前或同时发生。
研究人员证明，在胰腺炎合并PDAC（ptPDAC）中，抗原递呈I型常规树突状细胞（cDC1）被特异性激活。免疫检查点阻断疗法（iCBT）可导致细胞毒性CD8+ T细胞活化并消除ptPDAC，即使在PDAC再次复发时也能恢复寿命。使用PDAC抗原负载的cDC1作为疫苗，免疫治疗耐药的PDAC对iCBT变得敏感，肿瘤被消除。
这项研究确定了并发或未并发胰腺炎的PDAC免疫微环境的根本差异，并为将cDC1疫苗接种与iCBT结合作为一种潜在的治疗方案提供了理论依据。
附：英文原文
Title: Type I conventional dendritic cells facilitate immunotherapy in pancreatic cancer
Author: Krishnan K. Mahadevan, Allison M. Dyevoich, Yang Chen, Bingrui Li, Hikaru Sugimoto, Amari M. Sockwell, Kathleen M. McAndrews, Lakshmi Kavitha Sthanam, Huamin Wang, Shabnam Shalapour, Stephanie S. Watowich, Raghu Kalluri
Issue&Volume: 2024-06-28
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.
DOI: adh4567
Source: https://www.science.org/doi/10.1126/science.adh4567