Repurposing Cardiac Glycosides to Potentiate CD47 Blockade through Calreticulin-mediated Phagocytic Effects for Lung Cancer Treatment.

ABSTRACT: The abundance of macrophages within the tumor microenvironment (TME) of lung cancer represents a noteworthy therapeutic target. Exploiting the phagocytic function of macrophages by blocking the "don't eat me" signal, CD47, has shown significant therapeutic potential. However, novel CD47-targeted combination strategies warrant further investigation. Through an analysis of data obtained from a screening model focused on the macrophage-mediated killing effect, two cardiac glycosides (CGs), ouabain and digoxin, are shown to increase the capacity of macrophages to kill cancer cells after combination with CD47 antibody. Compared with the control, the combination strategy reduced the tumor volume in different lung cancer models and increased the macrophage phagocytosis rate ≈5-fold. Mechanistical

SUBMITTER: Ye ZH 

PROVIDER: S-EPMC12697853 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature