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 Silva 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
Affiliations
Vanessa Azevedo Voltarelli
Molecular Oncology Center, Sírio-Libanês Hospital, São Paulo, SP, Brazil; School of Physical Education and Sport, University of São Paulo, São Paulo, SP, Brazil; Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Corresponding author
Mariane Tami Amano
Molecular Oncology Center, Sírio-Libanês Hospital, São Paulo, SP, Brazil
Gabriel Cardial Tobias
School of Physical Education and Sport, University of São Paulo, São Paulo, SP, Brazil; Department of Pediatrics, Weill Cornell Medical College, New York, NY, USA
Gabriela Silva Borges
School of Physical Education and Sport, University of São Paulo, São Paulo, SP, Brazil
Ailma Oliveira da Paixão
School of Physical Education and Sport, University of São Paulo, São Paulo, SP, Brazil
Marcelo Gomes Pereira
School of Physical Education and Sport, University of São Paulo, São Paulo, SP, Brazil; Leeds School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, UK
Niels Olsen Saraiva Câmara
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
Waldir Caldeira
Department of Genetics and Evolutionary Biology, University of São Paulo, São Paulo, SP, Brazil
Alberto Freitas Ribeiro
Department of Genetics and Evolutionary Biology, University of São Paulo, São Paulo, SP, Brazil
Leo Edmond Otterbein
Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Carlos Eduardo Negrão
School of Physical Education and Sport, University of São Paulo, São Paulo, SP, Brazil; Heart Institute, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil
James Edward Turner
Department for Health, University of Bath, Bath, UK; School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK
Patricia Chakur Brum
School of Physical Education and Sport, University of São Paulo, São Paulo, SP, Brazil; Department of Physiology & Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
Anamaria Aranha Camargo
Molecular Oncology Center, Sírio-Libanês Hospital, São Paulo, SP, Brazil
Summary: 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.
