Distinct myeloid antigen-presenting cells dictate differential fates of tumor-specific CD8+ T cells in pancreatic cancer

• DOI: 10.1172/jci.insight.151593
• Publication Date: 2022-04-08T12:36:17Z
• Authors: Adam L. Burrack; Zoe C. Schmiechen; Michael T. Patterson; Ebony A. Miller; Ellen J. Spartz; Meagan R. Rollins; Jackson F. Raynor; Jason S. Mitchell; Tsuneyasu Kaisho; Brian T. Fife; Ingunn M. Stromnes
• Keywords: Cancer Immunotherapy; Priming (agriculture); Pancreatic tumor

We investigate how myeloid subsets differentially shape immunity to pancreatic ductal adenocarcinoma (PDA). show that tumor antigenicity sculpts cell composition and functionality. Antigenicity promotes accumulation of type 1 dendritic cells (cDC1), which is driven by Xcr1 signaling, overcomes macrophage-mediated suppression. The therapeutic activity adoptive T therapy or programmed death ligand blockade required cDC1s, sustained splenic Klrg1+ cytotoxic antitumor functional intratumoral cells. KLRG1 cDC1 genes correlated in human tumors, PDA patients with high survived longer than low KLRG1. immunotherapy CD40 agonist also host cDC1s for maximal benefit. However, exhibited partial benefit cDC1-deficient hosts resulted priming tumor-specific yet atypical CD8+ a regulatory phenotype failed participate control. Monocyte/macrophage depletion using clodronate liposomes abrogated enhanced the via engagement innate immunity. In sum, our study supports are essential sustaining effective differential roles monocytes/macrophages instructing fate response.