Moderate-intensity aerobic exercise training improves CD8+ tumor-infiltrating lymphocytes effector function by reducing mitochondrial loss
Vanessa Azevedo Voltarelli, Mariane Tami Amano, Gabriel Cardial Tobias, Gabriela S. Borges, Ailma Oliveira da Paixão, Marcelo Gomes Pereira, Niels Olsen Saraiva Câmara, Waldir Caldeira, Alberto Freitas Ribeiro, Leo Edmond Otterbein, Carlos Eduardo Negrão, James Edward Turner, Patricia Chakur Brum, Anamaria Aranha Camargo
Abstract
Aerobic exercise training (AET) has emerged as a strategy to reduce cancer mortality, however, the mechanisms explaining AET on tumor development remain unclear. Tumors escape immune detection by generating immunosuppressive microenvironments and impaired T cell function, which is associated with T cell mitochondrial loss. AET improves mitochondrial content and function, thus we tested whether AET would modulate mitochondrial metabolism in tumor-infiltrating lymphocytes (TIL). Balb/c mice were subjected to a treadmill AET protocol prior to CT26 colon carcinoma cells injection and until tumor harvest. Tissue hypoxia, TIL infiltration and effector function, and mitochondrial content, morphology and function were evaluated. AET reduced tumor growth, improved survival, and decreased tumor hypoxia. An increased CD8 + TIL infiltration, IFN-γ and ATP production promoted by AET was correlated with reduced mitochondrial loss in these cells. Collectively, AET decreases tumor growth partially by increasing CD8 + TIL effector function through an improvement in their mitochondrial content and function.