Newswise — WASHINGTON, D.C. (May 3, 2015) — 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 (GBM) 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 phagocytosis (process of ingesting particles by a cell) 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 — a type of white blood cell that helps digest foreign cellular debris— is heterogeneous, encompassing M1, pro-inflammatory macrophages, and M2, pro-tumoral 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 GBM 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 percent) than that observed in mice in the control group (33.7 percent).
Author Block: Suzana Kahn, PhD; Tej Azad; Siddhartha Mitra, PhD; Sharareh Gholamin, MD; Samuel H. Cheshier, MD, PhD.
Disclosure: The author reported no conflicts of interest.
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About the 2015 AANS Annual Scientific Meeting: Attended by neurosurgeons, neurosurgical residents, medical students, neuroscience nurses, clinical specialists, physician assistants, allied health professionals and other medical professionals, the AANS Annual Scientific Meeting is the largest gathering of neurosurgeons in the nation, with an emphasis on the field’s latest research and technological advances. More than 1,200 scientific abstracts were presented for review at the 2015 AANS Annual Scientific Meeting, and the scientific presentations given at this year’s event represent cutting-edge examples of the incredible developments taking place within the field of neurosurgery. Additional information about the 2015 AANS Annual Scientific Meeting and the meeting program can be found here.
Founded in 1931 as the Harvey Cushing Society, the American Association of Neurological Surgeons (AANS) is a scientific and educational association with more than 9,000 members worldwide. The AANS is dedicated to advancing the specialty of neurological surgery in order to provide the highest quality of neurosurgical care to the public. Fellows of the AANS are board-certified by the American Board of Neurological Surgery, the Royal College of Physicians and Surgeons of Canada, or the Mexican Council of Neurological Surgery, A.C. Neurosurgery is the medical specialty concerned with the prevention, diagnosis, treatment and rehabilitation of disorders that affect the spinal column, spinal cord, brain, nervous system and peripheral nerves.
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