Anti-cd47 treatment potentiates phagocytosis of medulloblastoma by m1 polarized macrophages following irradiation

Abstract Medulloblastoma (MB) is the most common malignant brain tumor of childhood and accounts for 15–20% of all pediatric brain tumors. Despite significant advancements over the last decade in our understanding of the molecular underpinnings of MB, the overall risk of recurrence remains high, prognosis remains poor, and available treatment modalities remain limited for patients with this disease. Accordingly, the area of targeting tumor immune resistance has garnered increasing interest as a potentially safe and effective adjunctive therapy. CD47 is a cell surface protein that acts as a primary “don’t eat me” signal to the innate immune system and has been shown to be crucial in allowing tumor cells to evade phagocytosis by tumor-associated macrophages. Several preclinical studies aimed at blocking this “don’t eat me signal” through the application of a mouse anti-human monoclonal antibody (Ab) to CD47 (anti-CD47) have shown promise in pediatric brain tumor models. Further, chemotherapy and irradiation have been shown to increase the expression of pro-phagocytic signals on the surfaces of tumor cells. The authors examined the use of anti-CD47 Ab on the rates of phagocytosis of MB cells undergoing different single-fraction doses of external beam irradiation in vitro. The use of anti-CD47 Ab in the D425 MB cell line phagocytosis assay significantly increased rates of phagocytosis for 0 Gy (4.1% without vs. 20.3% with anti-CD47 Ab; p < 0.0001), 2 Gy (7.4% without vs. 23.4% with anti-CD47 Ab; p < 0.0001), 5 Gy (11.9% without vs. 27.3% with anti-CD47 Ab; p < 0.0001), 10 Gy (21.7% without vs. 34% with anti-CD47 Ab; p < 0.0001), and 20 Gy treatment groups (27.2% without vs. 43.9% with anti-CD47 Ab; p < 0.0001). A similar pattern of phagocytosis potentiation through use of anti-CD47 Ab with increasing doses of radiation was seen in D458 and D341 MB cell lines.