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Effect of immune modulation on the skeletal muscle mitochondrial exercise response: An exploratory study in mice with cancer

Cancer causes mitochondrial alterations in skeletal muscle, which may progress to muscle wasting and, ultimately, to cancer cachexia. Understanding how exercise adaptations are altered by cancer and cancer treatment is important for the effective design of exercise interventions aimed at improving c...

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Autores principales: Buss, Linda A., Hock, Barry, Merry, Troy L., Ang, Abel D., Robinson, Bridget A., Currie, Margaret J., Dachs, Gabi U.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525738/
https://www.ncbi.nlm.nih.gov/pubmed/34665826
http://dx.doi.org/10.1371/journal.pone.0258831
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author Buss, Linda A.
Hock, Barry
Merry, Troy L.
Ang, Abel D.
Robinson, Bridget A.
Currie, Margaret J.
Dachs, Gabi U.
author_facet Buss, Linda A.
Hock, Barry
Merry, Troy L.
Ang, Abel D.
Robinson, Bridget A.
Currie, Margaret J.
Dachs, Gabi U.
author_sort Buss, Linda A.
collection PubMed
description Cancer causes mitochondrial alterations in skeletal muscle, which may progress to muscle wasting and, ultimately, to cancer cachexia. Understanding how exercise adaptations are altered by cancer and cancer treatment is important for the effective design of exercise interventions aimed at improving cancer outcomes. We conducted an exploratory study to investigate how tumor burden and cancer immunotherapy treatment (anti-PD-1) modify the skeletal muscle mitochondrial response to exercise training in mice with transplantable tumors (B16-F10 melanoma and EO771 breast cancer). Mice remained sedentary or were provided with running wheels for ~19 days immediately following tumor implant while receiving no treatment (Untreated), isotype control antibody (IgG2a) or anti-PD-1. Exercise and anti-PD-1 did not alter the growth rate of either tumor type, either alone or in combination therapy. Untreated mice with B16-F10 tumors showed increases in most measured markers of skeletal muscle mitochondrial content following exercise training, as did anti-PD-1-treated mice, suggesting increased mitochondrial content following exercise training in these groups. However, mice with B16-F10 tumors receiving the isotype control antibody did not exhibit increased skeletal muscle mitochondrial content following exercise. In untreated mice with EO771 tumors, only citrate synthase activity and complex IV activity were increased following exercise. In contrast, IgG2a and anti-PD-1-treated groups both showed robust increases in most measured markers following exercise. These results indicate that in mice with B16-F10 tumors, IgG2a administration prevents exercise adaptation of skeletal muscle mitochondria, but adaptation remains intact in mice receiving anti-PD-1. In mice with EO771 tumors, both IgG2a and anti-PD-1-treated mice show robust skeletal muscle mitochondrial exercise responses, while untreated mice do not. Taken together, we postulate that immune modulation may enhance skeletal muscle mitochondrial response to exercise in tumor-bearing mice, and suggest this as an exciting new avenue for future research in exercise oncology.
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spelling pubmed-85257382021-10-20 Effect of immune modulation on the skeletal muscle mitochondrial exercise response: An exploratory study in mice with cancer Buss, Linda A. Hock, Barry Merry, Troy L. Ang, Abel D. Robinson, Bridget A. Currie, Margaret J. Dachs, Gabi U. PLoS One Research Article Cancer causes mitochondrial alterations in skeletal muscle, which may progress to muscle wasting and, ultimately, to cancer cachexia. Understanding how exercise adaptations are altered by cancer and cancer treatment is important for the effective design of exercise interventions aimed at improving cancer outcomes. We conducted an exploratory study to investigate how tumor burden and cancer immunotherapy treatment (anti-PD-1) modify the skeletal muscle mitochondrial response to exercise training in mice with transplantable tumors (B16-F10 melanoma and EO771 breast cancer). Mice remained sedentary or were provided with running wheels for ~19 days immediately following tumor implant while receiving no treatment (Untreated), isotype control antibody (IgG2a) or anti-PD-1. Exercise and anti-PD-1 did not alter the growth rate of either tumor type, either alone or in combination therapy. Untreated mice with B16-F10 tumors showed increases in most measured markers of skeletal muscle mitochondrial content following exercise training, as did anti-PD-1-treated mice, suggesting increased mitochondrial content following exercise training in these groups. However, mice with B16-F10 tumors receiving the isotype control antibody did not exhibit increased skeletal muscle mitochondrial content following exercise. In untreated mice with EO771 tumors, only citrate synthase activity and complex IV activity were increased following exercise. In contrast, IgG2a and anti-PD-1-treated groups both showed robust increases in most measured markers following exercise. These results indicate that in mice with B16-F10 tumors, IgG2a administration prevents exercise adaptation of skeletal muscle mitochondria, but adaptation remains intact in mice receiving anti-PD-1. In mice with EO771 tumors, both IgG2a and anti-PD-1-treated mice show robust skeletal muscle mitochondrial exercise responses, while untreated mice do not. Taken together, we postulate that immune modulation may enhance skeletal muscle mitochondrial response to exercise in tumor-bearing mice, and suggest this as an exciting new avenue for future research in exercise oncology. Public Library of Science 2021-10-19 /pmc/articles/PMC8525738/ /pubmed/34665826 http://dx.doi.org/10.1371/journal.pone.0258831 Text en © 2021 Buss et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Buss, Linda A.
Hock, Barry
Merry, Troy L.
Ang, Abel D.
Robinson, Bridget A.
Currie, Margaret J.
Dachs, Gabi U.
Effect of immune modulation on the skeletal muscle mitochondrial exercise response: An exploratory study in mice with cancer
title Effect of immune modulation on the skeletal muscle mitochondrial exercise response: An exploratory study in mice with cancer
title_full Effect of immune modulation on the skeletal muscle mitochondrial exercise response: An exploratory study in mice with cancer
title_fullStr Effect of immune modulation on the skeletal muscle mitochondrial exercise response: An exploratory study in mice with cancer
title_full_unstemmed Effect of immune modulation on the skeletal muscle mitochondrial exercise response: An exploratory study in mice with cancer
title_short Effect of immune modulation on the skeletal muscle mitochondrial exercise response: An exploratory study in mice with cancer
title_sort effect of immune modulation on the skeletal muscle mitochondrial exercise response: an exploratory study in mice with cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525738/
https://www.ncbi.nlm.nih.gov/pubmed/34665826
http://dx.doi.org/10.1371/journal.pone.0258831
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