Data Supplement from Macrophage-Derived Granulin Drives Resistance to Immune Checkpoint Inhibition in Metastatic Pancreatic Cancer

Files in this Data Supplement: - Supplementary Figures. Figure S1: Loss of CD8+ T cell numbers during metastatic progression in PDAC patients and genetically engineered mouse model of pancreatic cancer. Figure S2: Colony stimulating factor 1 (CSF-1) is expressed by disseminated PDAC cells, and its cognate receptor CSF-1R is expressed by metastasis associated macrophages. Figure S3: Pharmacological blockade of CSF-1R using BLZ945 reprograms MAMs, restores T cell infiltration, and reduces metastasis. Figure S4: CSF-1 inhibition reduces desmoplasia, enhances CD8+ T cell infiltration and sensitizes metastatic PDAC to αPD-1 treatment. Figure S5: Administration of Digoxin, a transcriptional inhibitor of HIF-1α, promotes M1-like MAM reprogramming and reduces Granulin level in vivo. Figure S6: αPD-1 therapy dramatically reduces metastatic tumor burden in the absence of granulin, an effect which depends on a high abundance of immune stimulatory MAMs. Figure S7: Reduction in liver fibrosis improves CD8+ T cell infiltration and enhances αPD-1 therapy in metastatic pancreatic cancer. Figure S8: Macrophage-derived granulin drives resistance to immune checkpoint inhibition in metastatic pancreatic cancer.