IL-15 Complex Enhances Agonistic Anti-CD40 + Anti-PDL1 by Correcting the T-bet to Tox Ratio in CD8+ T cells Infiltrating Pancreatic Ductal Adenocarcinoma.

ABSTRACT: Agonistic anti-CD40 with anti-PD-1 can elicit objective responses in a small number of patients with pancreatic ductal adenocarcinoma (PDA). Better understanding of their individual effects on the pancreatic tumor microenvironment will help inform new strategies to further improve outcomes. In this study, we map tumor-specific CD8+ T-cell differentiation following agonistic anti-CD40 and/or anti-PDL1 in PDA. Rare Tcf1+Slamf6+ tumor-specific CD8+ T cells are identified and likely seed memory precursors that transition into exhausted or effector T cells. In tumors, anti-PDL1 drove the clonal expansion of Gzmk+ progenitor exhausted CD8+ T cells, whereas anti-CD40 promoted CD4+ T-cell clonal expansion and accumulation of Tcf1+Slamf6+ CD8+ T cells. Cloning the most frequent intratumoral T-cell

SUBMITTER: Schmiechen ZC 

PROVIDER: S-EPMC12134750 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature