Repolarization of Tumor-Associated Macrophages (TAMs) towards M1 anti-tumor macrophages in Acute Myeloid Leukemia: a murine model

• Grant number: 20/16739-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): November 01, 2021
• Effective date (End): April 30, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Eduardo Magalhães Rego
• Grantee: Lucio Henrique Sousa Pinheiro
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Acute Myeloid Leukemia (AML) is a malignant hematological disorder driven by unregulated proliferation and impaired differentiation of myeloid progenitor cells. The most common treatment for AML is the conventional chemotherapy based on the combination of an anthracycline and cytarabine, leading to several side effects, which may affect the treatment progress. To design new therapeutic approaches is necessary to understand the pathogenesis and the immune system involvement in leukemogenesis regulation. Macrophages are phagocytic immune cells that play important roles in tumor eradication, and conversely, in Cancer initiation and progression. Macrophages are classified into two distinct subsets according to their function, M1 macrophages holding pro-inflammatory functions and M2 macrophages bearing anti-inflammatory properties. Macrophage polarization is mediated by cytokines, microRNAs, and other mediators released in the microenvironment that trigger these cells to present their respective roles. Since M2 macrophages have anti-inflammatory features, they are able to promote cell proliferation, angiogenesis, and consequently, tumor progression. Tumor-Associated Macrophages (TAMs) present M2-like phenotype, being involved in tumor growth, metastasis and chemoresistance. Macrophage reprogramming efforts have demonstrated that TAM-M2 can be repolarized towards M1 anti-tumor macrophages via microRNAs delivery systems becoming a potential therapeutic strategy. Taking in this regard, we intend to conduct the repolarization of TAM-M2 to the M1 subtype in a murine model of AML, employing microRNAs via a delivery system. (AU)