Prostaglandin E2: modulator of the glycolytic pathway during efferocytosis of apoptotic tumor cells by dendritic cells

• Grant number: 25/05706-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2025
• End date: February 28, 2027
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Alexandra Ivo de Medeiros
• Grantee: Luiza Maria Fernandes
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Prostaglandin E2 (PGE2) is a lipid mediator produced by several cell types, exerting itseffector functions through autocrine and paracrine mechanisms. PGE2 synthesis canoccur constitutively and/or be induced via activating cyclooxygenase enzymes 1 and 2(COX-1 and COX-2), both under physiological conditions and in the context of infectionsor pathological processes. Previous studies have demonstrated that PGE2 is one of thekey mediators released during phagocytes' clearance of apoptotic cells, a processknown as efferocytosis. In the tumor microenvironment, conventional treatments suchas radiotherapy and chemotherapy can induce tumor cell apoptosis, and thesubsequent removal of those cells by phagocytes promotes tumor progression. Ourpreliminary data has shown that the efferocytosis of apoptotic glioblastoma cells leadsto a decrease in MHC-II expression, an increase in PDL-1, and the production ofmediators such as IL-10, TGF-B, and PGE2 by dendritic cells, thereby promoting atolerogenic immune profile. In the last few years, interest has been growing inunderstanding the impact of efferocytosis on the cellular metabolism of macrophagesand dendritic cells, particularly focusing on how metabolic pathways shape phagocytefunction. Our findings indicate that the efferocytosis of apoptotic tumor cells enhancesPGE2 production, lactate levels, and GLUT-1 expression, suggesting early activation ofthe glycolytic pathway following efferocytosis. However, the role of PGE2 in modulatingmetabolic processes during the efferocytosis of apoptotic cells remains unknown.Therefore, this project aims to investigate the role of PGE2 in activating the glycolyticpathway in dendritic cells following the efferocytosis of apoptotic glioblastoma cells andits contribution to maintaining the tolerogenic profile of these cells.