Data Supplement from Macrophage-Derived Granulin Drives Resistance to Immune Checkpoint Inhibition in Metastatic Pancreatic Cancer
Year: 2023
Type: other
Abstract: 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.
Authors: Valeria Quaranta, Carolyn Rainer, Sebastian R. Nielsen, Meirion L. Raymant, Muhammad S. Ahmed, Dannielle D. Engle, Arthur Taylor, Trish Murray, Fiona Campbell, Daniel H. Palmer, David A. Tuveson, Ainhoa Mielgo, Michael C. Schmid
Language: English
Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4361848908