Analysis of the polarization of human macrophages induced by the secretome of chemoresistant and metastatic breast cancer cells.

• Grant number: 23/15660-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2024
• End date: May 31, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Claudiana Lameu
• Grantee: Gabriel Batista de Souza
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The aim of this study is to analyze the polarization of human macrophages induced bythe secretome of chemoresistant and metastatic breast cancer cells, in order to understand therelationship between the tumor microenvironment, especially tumor-associated macrophages,and chemoresistance and metastasis. Understanding this relationship is fundamental for thedevelopment of new therapeutic approaches, since resistance to multiple drugs is one of themain reasons for the failure of conventional and/or systemic chemotherapy in cases of breastcancer. The project includes a brief literature review on the subject, a description of themethods used, an analysis and comparison of the results obtained and a discussion of theimplications of the findings for breast cancer research. Although previous studies indicate thatchemoresistant and metastatic cells can lead to an M2 phenotype, which is associated with amore immunosuppressive tumor environment, macrophages in the tumor microenvironmentcan assume different states of activation and polarization, which can have significant anddiverse impacts on cancer development and progression. Therapeutic strategies are beingdeveloped to modulate the polarization of macrophages in the tumour microenvironment inorder to improve the efficacy of cancer treatment by promoting a more robust immuneresponse against cancer cells. Therefore, knowing the phenotypic profile of macrophages inthe context of chemoresistance and metastasis should be important for the development oftargeted therapies, immunotherapies and other approaches to rebalance the macrophagepolarization spectrum in favor of the anti-tumor response. Thus, the analysis of macrophagepolarization induced by the secretome of chemoresistant and metastatic cells is the main area of analysis of this research.