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Lactate Potentiates Differentiation and Expansion of Cytotoxic T Cells

44 Pages Posted: 28 Jun 2019 Sneak Peek Status: Review Complete

See all articles by Helene Rundqvist

Helene Rundqvist

Karolinska Institutet - Department of Cell and Molecular Biology

Pedro Velica

Karolinska Institutet - Department of Cell and Molecular Biology

Laura Barbieri

Karolinska Institutet - Department of Cell and Molecular Biology

Paulo Gameiro

Francis Crick Institute

Pedro P. Cunha

University of Cambridge

Milos Gojkovic

Karolinska Institutet - Department of Cell and Molecular Biology

David Bargiela

University of Cambridge

Sara Mijwel

Karolinska Institutet - Department of Cell and Molecular Biology

Emil Ahlstedt

Karolinska Institutet - Department of Cell and Molecular Biology

Iosifina Foskolou

Karolinska Institutet - Department of Cell and Molecular Biology

Maria Victoria Ruiz-Perez

Karolinska Institutet - Department of Microbiology, Tumor and Cell Biology (MTC)

Marie Arsenian-Henriksson

Karolinska Institutet - Department of Microbiology, Tumor and Cell Biology (MTC)

Jernej Ule

University of Cambridge - MRC Laboratory of Molecular Biology

Arne Östman

Karolinska Institutet - Department of Oncology-Pathology

Randall S. Johnson

Karolinska Institutet - Department of Cell and Molecular Biology

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Abstract

Exercise has a wide range of systemic effects. In animal models, repeated exertion reduces malignant tumor progression, and clinically, exercise can improve outcome for cancer patients. The etiology of the effect of exercise on tumor progression is unclear, as are the cellular actors involved. We show here that exercise-induced reduction in tumor growth is dependent on CD8+ T cells and that lactate, which is produced at high levels during exertion, increases proliferative capacity and cytotoxicity of CD8+ T cells. We found that at elevated levels lactate is used as a fuel during T cell activation. We further found that daily injections of lactate into animals can reduce malignant tumor growth in a dose- and CD8+ T cell-dependent manner. These data demonstrate that lactate can act to enhance expansion of cytotoxic T cells and in so doing reduce cancer progression.

Keywords: Exercise, immunotherapy, Lactate, Metabolism

Suggested Citation

Rundqvist, Helene and Velica, Pedro and Barbieri, Laura and Gameiro, Paulo and Cunha, Pedro P. and Gojkovic, Milos and Bargiela, David and Mijwel, Sara and Ahlstedt, Emil and Foskolou, Iosifina and Ruiz-Perez, Maria Victoria and Arsenian-Henriksson, Marie and Ule, Jernej and Östman, Arne and Johnson, Randall S., Lactate Potentiates Differentiation and Expansion of Cytotoxic T Cells (June 28, 2019). CELL-METABOLISM-D-19-00670. Available at SSRN: https://ssrn.com/abstract=3411249 or http://dx.doi.org/10.2139/ssrn.3411249
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Helene Rundqvist

Karolinska Institutet - Department of Cell and Molecular Biology

Granits väg 4
SE-171 77 Stockholm, Stockholm 17171
Sweden

Pedro Velica

Karolinska Institutet - Department of Cell and Molecular Biology

Granits väg 4
SE-171 77 Stockholm, Stockholm 17171
Sweden

Laura Barbieri

Karolinska Institutet - Department of Cell and Molecular Biology

Granits väg 4
SE-171 77 Stockholm, Stockholm 17171
Sweden

Paulo Gameiro

Francis Crick Institute ( email )

1 Midland Road
London, NW1 1AT
United Kingdom

Pedro P. Cunha

University of Cambridge

Trinity Ln
Cambridge, CB2 1TN
United Kingdom

Milos Gojkovic

Karolinska Institutet - Department of Cell and Molecular Biology

Granits väg 4
SE-171 77 Stockholm, Stockholm 17171
Sweden

David Bargiela

University of Cambridge ( email )

Trinity Ln
Cambridge, CB2 1TN
United Kingdom

Sara Mijwel

Karolinska Institutet - Department of Cell and Molecular Biology

Granits väg 4
SE-171 77 Stockholm, Stockholm 17171
Sweden

Emil Ahlstedt

Karolinska Institutet - Department of Cell and Molecular Biology

Granits väg 4
SE-171 77 Stockholm, Stockholm 17171
Sweden

Iosifina Foskolou

Karolinska Institutet - Department of Cell and Molecular Biology

Granits väg 4
SE-171 77 Stockholm, Stockholm 17171
Sweden

Maria Victoria Ruiz-Perez

Karolinska Institutet - Department of Microbiology, Tumor and Cell Biology (MTC)

Solnavägen 9
Solna, 171 65
Sweden

Marie Arsenian-Henriksson

Karolinska Institutet - Department of Microbiology, Tumor and Cell Biology (MTC)

Solnavägen 9
Solna, 171 65
Sweden

Jernej Ule

University of Cambridge - MRC Laboratory of Molecular Biology ( email )

Cambridge Biomedical Campus
Francis Crick Avenue
Cambridge, CB2 0QH
United Kingdom

Arne Östman

Karolinska Institutet - Department of Oncology-Pathology

171 16 Stockholm
Sweden

Randall S. Johnson (Contact Author)

Karolinska Institutet - Department of Cell and Molecular Biology ( email )

Granits väg 4
SE-171 77 Stockholm, Stockholm 17171
Sweden

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