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.

中文翻译：

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I 型传统树突状细胞促进胰腺癌的免疫治疗


与胰腺炎相关的炎症和组织损伤可能先于胰腺导管腺癌（PDAC）发生，也可能与胰腺导管腺癌（PDAC）同时发生。我们证明，在伴有胰腺炎的 PDAC (ptPDAC) 中，抗原呈递 I 型常规树突状细胞 (cDC1s) 被特异性激活。免疫检查点阻断疗法 (iCBT) 会导致细胞毒性 CD8 + T 细胞激活并消除 ptPDAC，甚至在 PDAC 再次攻击后也能恢复寿命。使用负载 PDAC 抗原的 cDC1 作为疫苗，免疫治疗耐药的 PDAC 对 iCBT 敏感，并消除了肿瘤。 cDC1 疫苗接种与 iCBT 相结合，确定了肿瘤浸润 CD8 + T 细胞中具有潜在治疗重要性的特定 CDR3 序列。这项研究确定了患有或不患有胰腺炎的 PDAC 中免疫微环境的根本差异，并为将 cDC1 疫苗接种与 iCBT 结合作为潜在的治疗选择提供了理由。