The contribution given by the aerobic physical activity to the antitumor immune response

Author(s)

Gabriel Cardial Tobias

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Escola de Educação Física e Esportes (EEFE/BT)
• Defense date: 2017-10-24

Examining board members

Patricia Chakur Brum; Roger Chammas; Edilamar Menezes de Oliveira; Elaine Guadelupe Rodrigues

• Advisor: Patricia Chakur Brum

Abstract

It is already very well accepted that the aerobic physical activity reduces the incidence of many different types of cancer and mitigates the tumor progression. However, there is an investigation gap on the literature about the mechanisms underlying this response. Recently, a body of literature has arisen which show the importance of maintain antitumoral immune response to mitigated tumor progression, and strategy for enhance this response remains a major challenge. Presently, we demonstrate that the aerobic physical activity has the potential to modulate antitumor immune responses. Firstly, we have observed that the aerobic physical activity mitigated the tumor progression in three different animal models of cancer and increased survival in the animals which had B16F10 melanoma. Moreover, we have observed that the aerobic physical activity also seems modulate the tumor infiltrating T lymphocytes (TILs-T) and the tumor associated macrophages (TAMs) in as specific-tumor way. Based on the computer gene set enrichment analysis (GSEA), we have observed that the previous aerobic physical activity helped to develop an immunological signature of the tumor shared among patients with different cancer etiologies with higher survival over time. This signature introduced us to some genes that are associated with a higher survival over time when increased in tumors of patients with melanoma, breast cancer and lymphoma. The GSEA analysis also shows that the aerobic physical activity is able to introduce an immune signature similar to the one observed in animals with B16F10 melanoma sensitive to the immunotherapic anti- cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) and patients post treatment with anti-CTLA-4. This immune signature also revealed genes with a strong association with high survival over time. This immune signature also revealed genes associated with a higher survival over time when their expression were increased in melanoma patients. In conclusion, aerobic physical activity is a powerful tool to counteract tumor progression due to its capacity to modulate antitumor immune responses (AU)

• FAPESP's process: 14/25830-9 - Contribution of voluntary aerobic physical activity on cancer cachexia mediators in mice
• Grantee: Gabriel Cardial Tobias
• Support Opportunities: Scholarships in Brazil - Master