Analysis of the microglial profile, proliferation, metastasis, and autophagy in the tumor microenvironment and adjacent areas in a preclinical model of diffuse intrinsic pontine glioma.

• Grant number: 25/04131-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2025
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Rosana de Lima Pagano
• Grantee: Leandro Kaoru Shoji
• Host Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil

Abstract

The diffuse intrinsic pontine glioma (DIPG) is recognized as one of the greatest challenges in modern neuro-oncology, both for neurosurgeons and researchers. It is a lethal pediatric brain tumor with a median survival of approximately 12 months, remaining untreatable due to its infiltrative nature, complex anatomical location, and well-preserved blood-brain barrier (BBB). In this context, oncological neuroscience investigates the mechanisms by which glioma cells recruit, manipulate, and utilize other normal non-neoplastic cells, including endothelial cells, astrocytes, and immune cells (microglia), to create a complex and dynamic tumor microenvironment (TME), which has been increasingly recognized as a crucial factor in DIPG progression. For decades, the lack of knowledge about the molecular biology, cellular mechanisms, and TME of DIPG has hindered treatment advancements, with no impact on patients' survival or quality of life. Therefore, deciphering these molecular interactions within the TME may be crucial for developing new therapies. Our project aims to better understand the TME and adjacent areas, focusing on the inflammatory activation profile of microglia, as well as the proliferation, metastasis, and autophagy processes involved in tumorigenesis in a murine experimental model of DIPG. To achieve this, we will evaluate the expression patterns of microglia/macrophage markers (CD68 and CD163) and cellular markers related to tumor proliferation (EGF and VEGF), metastasis (MMP2 and MMP9), and autophagic dysregulation (Bcl-2) using immunohistochemistry assays. We believe our findings may contribute to a better understanding of the tumor microenvironment, ultimately aiding in the development of new multi-target therapeutic strategies. (AU)