biostudies-literatureStromnes IMAACRAmerican Cancer SocietyNIAID NIH HHSPancreatic Cancer Action NetworkNational Cancer InstituteNCI NIH HHSGiles W. and Elise G. Mead FoundationCancer Center977-989https://www.ebi.ac.uk/biostudies/studies/S-EPMC6548612biostudies-literatureUnknown7(6)Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy resistant to therapies, including immune-checkpoint blockade. We investigated two distinct strategies to modulate tumor-associated macrophages (TAM) to enhance cellular therapy targeting mesothelin in an autochthonous PDA mouse model. Administration of an antibody to colony-stimulating factor (anti-Csf1R) depleted Ly6C^low protumorigenic TAMs and significantly enhanced endogenous T-cell intratumoral accumulation. Despite increasing the number of endogenous T cells at the tumor site, as previously reported, TAM depletion had only minimal impact on intratumoral accumulation and persistence of T cells engineered to express a murine mesothelin-specific T-cell receptor (TCR). TAM depletion interfered with the antitumor actiCancer immunology researchDifferential Effects of Depleting versus Programming Tumor-Associated Macrophages on Engineered T Cells in Pancreatic Ductal Adenocarcinoma.PMC6548612P30 CA015704CA018029R01 CA161112124166-IRG-58-001-55-IRG65CA033084P30CA015704CA161112T35 AI118620P01 CA018029R37 CA03308417-20-25-STRO16-65-GREER01 CA033084Raynor JFGreenberg PDSpartz EJPierce RHHingorani SRBurrack ALHulbert ABrockenbrough JSStromnes IMBlack CBonson PfalseDifferential Effects of Depleting versus Programming Tumor-Associated Macrophages on Engineered T Cells in Pancreatic Ductal Adenocarcinoma.Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy resistant to therapies, including immune-checkpoint blockade. We investigated two distinct strategies to modulate tumor-associated macrophages (TAM) to enhance cellular therapy targeting mesothelin in an autochthonous PDA mouse model. Administration of an antibody to colony-stimulating factor (anti-Csf1R) depleted Ly6C^low protumorigenic TAMs and significantly enhanced endogenous T-cell intratumoral accumulation. Despite increasing the number of endogenous T cells at the tumor site, as previously reported, TAM depletion had only minimal impact on intratumoral accumulation and persistence of T cells engineered to express a murine mesothelin-specific T-cell receptor (TCR). TAM depletion interfered with the antitumor acti2019-01-01T00:00:00Z2019 Jun2025-04-04T07:58:04.043Z2020-06-04T07:06:57ZS-EPMC65486123102803310.1158/2326-6066.cir-18-044810.1158/2326-6066.CIR-18-0448