Moderate-intensity aerobic exercise training improves CD8+ tumor-infiltrating lymphocytes effector function by reducing mitochondrial loss

• Published in: iScience Vol. 27; no. 6; p. 110121
• Main Authors: Voltarelli, Vanessa Azevedo, Amano, Mariane Tami, Tobias, Gabriel Cardial, Borges, Gabriela Silva, Oliveira da Paixão, Ailma, Pereira, Marcelo Gomes, Saraiva Câmara, Niels Olsen, Caldeira, Waldir, Ribeiro, Alberto Freitas, Otterbein, Leo Edmond, Negrão, Carlos Eduardo, Turner, James Edward, Brum, Patricia Chakur, Camargo, Anamaria Aranha
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.06.2024; Elsevier
• Subjects: Biochemistry; Biological sciences; Cancer systems biology; Immunology; Natural sciences; Physiology; Systems biology; Cancer systems biology; Immunology; Natural sciences; Systems biology; Biological sciences; Biochemistry; Physiology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.110121

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. [Display omitted] •Exercise training reduces tumor growth and improves survival in colorectal cancer•Trained mice present tumors with less hypoxia and higher CD8+ T cells infiltration•The production of IFNγ by CD8+ TIL is increased in exercise-trained mice•CD8+ TIL from trained mice show higher mitochondrial density and function Natural sciences; Biological sciences; Biochemistry; Physiology; Immunology; Systems biology; Cancer systems biology