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

• Grant number: 20/15317-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2021
• End date: March 31, 2024
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Roger Chammas
• Grantee: Lucas Evaristo Ferreira Flausino
• Host 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
• Associated scholarship(s): 22/01243-3 - Effect of initiating antihypertensive regimens associated with chemotherapy on pancreatic, colorectal and ovarian cancer outcomes: a Medicare SEER cohort analysis, BE.EP.IC

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).

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BALKRISHNAN, RAJESH; DESAI, RAJ P.; NARAYAN, ADITYA; CAMACHO, FABIAN T.; FLAUSINO, LUCAS E.; CHAMMAS, ROGER. Associations between initiating antihypertensive regimens on stage I-III colorectal cancer outcomes: A Medicare SEER cohort analysis. CANCER MEDICINE, v. 10, n. 15, JUN 2021. (20/15317-3, 15/22814-5)