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Exercise as a strategy to shift activation of tumor-associated macrophages

Grant number: 20/15317-3
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): March 01, 2021
Effective date (End): February 28, 2022
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Roger Chammas
Grantee:Lucas Evaristo Ferreira Flausino
Home Institution: Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). Coordenadoria de Serviços de Saúde (CSS). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The tumor microenvironment is composed of several barriers and obstacles that decrease the chemo-radiotherapeutic effectiveness of cancer treatment. One of these obstacles would be the aberrant and deficient vascular network, which limits tumor perfusion, preventing the total delivery of drugs and creating areas of tumor hypoxia. Another would be the presence of tumor-associated macrophages with a predominance of M2 profile (alternatively activated), which support tumor progression and evasion, discouraging the immune response, enabling the formation of new irregular vessels, and secreting factors that stimulate invasion and metastasis. On the other hand, literature data suggest that aerobic physical exercise can, directly and indirectly, interfere in this microenvironment, resulting in vascular normalization, less hypoxic areas, and favorable immunogenic shift on macrophage profile. This scientific initiation project aims to investigate, in a genetically modified murine model that overexpresses the PyMT oncoprotein for breast tumorigenesis, if the vascular, metabolic, and immunological consequences caused by physical activity, can modify the amount of M2 macrophages in the tumor, to reduce the progression of the disease. Also, we aim to investigate, on in vitro and in vivo models, the specificity of a new marker (Cy5-UNO-C) for CD206+ / MRC1+ cells, derived from the UNO peptide (CSPGAKVRC).