Stimulating the Resolution of Tumor Debris to Control Medulloblastoma

Background: Tumor recurrence occurs in one-third of patients with medulloblastoma. Current clinical approaches to reduce medulloblastoma tumor burden, including chemotherapy, may contribute to relapse by creating tumor cell debris. The debris of dead cancer cells can act as a source of tumor stimulation via inflammation. A new direction has emerged in inflammation research with the discovery of endogenous specialized pro-resolving lipid mediators. We hypothesize that resolvins and protectins represent a novel modality in medulloblastoma treatment by pharmacologically promoting the clearance of tumor debris. Results: Flow cytometry confirmed that the chemotherapy cisplatin and the targeted therapy JQ-1 generated medulloblastoma tumor cell debris. Chemotherapy- and targeted therapy-induced tumor debris stimulated primary tumor growth. Protectins enhanced macrophage phagocytosis of medulloblastoma tumor debris and counter-regulated secretion of pro-inflammatory cytokines. Medulloblastoma tumor progression re...