Winner of the Medical Student Summer Research Fellowship Award, Michael Zhang, presented his research, M1 Macrophages Demonstrate a Superior Phagocytic Response Against Glioblastoma Multiforme Following Anti-CD47 Treatment, during the 2015 American Association of Neurological Surgeons (AANS) Annual Scientific Meeting.
Glioblastoma multiforme is the most aggressive and common malignant primary brain tumor affecting adults. It is known to express CD47, which is an antigen that inhibits macrophage phagocytosi of the expressing cells. Previous studies have shown that mice transplanted with GBM tissue, and treated with anti-CD47 antibodies, survived longer. However, the macrophage population is heterogeneous, encompassing M1, proinflammatory macrophages, and M2, protumoral macrophages.
Results of the research indicate that in vitro disruption of the CD47-SIRPa signal induced a response from both M1 and M2 macrophages; however, the rate and responsiveness of phagocytosis by M1 macrophages was consistently greater. In addition, phenotypic evaluation of local macrophages surrounding transplanted GBM tissue in mice suggests that anti-CD47 treatment promotes a larger local M1 population.
During the study, researchers quantified the rate of phagocytosis of M1 and M2 mouse and human macrophages in vitro by flow cytometry. Each subtype was co-cultured with tumor cells, with or without anti-CD47 antibodies, and stained with identifying markers. Finally, they quantified in vivo the frequency of M1 macrophages present in the peritumoral space of mice xenografted with glioblastoma multiforme and randomized to a treatment regimen, with or without an anti-CD47 antibody.
The in vitro addition of anti-CD47 treatment significantly raised the M1 to M2 human macrophage phagocytosis rate ratio from 0.45 to 1.47, while also significantly elevating the rate of phagocytosis for both subtypes. In vivo, mice randomized to the treatment group presented with a peritumoral macrophage population that was significantly more M1-like (72.2%) than that observed in mice in the control group (33.7%).
Source: News Release
American Association of Neurological Surgeons
May 2, 2015