Impact of the mechanical properties of lymphoma cells on phagocytosis efficiency by macrophages

Macrophages, typically the most abundant immune cell in the tumor microenvironment, eliminate unwanted particles through phagocytosis, yet rarely internalize cancer cells. Antibody-based therapies are being developed to promote the elimination of tumoral cells via phagocytosis. Phagocytosis of lymphoma cells upon CD47-blockade requires the mechanosensitive integrin Mac-1; however, malignant cells often display reduced cellular stiffness. As aggressive lymphomas frequently exhibit loss-of-function mutations in the RhoA pathway, we hypothesize that these mutations reduce the stiffness of lymphoma cells, preventing their phagocytosis. Here, we show that mutations in the RhoA pathway of Burkitt lymphoma cells modify their actin cortex density and stiffness. Whereas RhoA mutations do not alter the expression of CD47 or Mac-1 ligands, they modulate the phagocytosis of lymphoma cells by macrophages in correlation with their stiffness. Overall, our findings suggest that loss-of-function mutations in the RhoA pathway reduce the stiffness of lymphoma cells and facilitate their escape from phagocytosis.