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: Linda A Buss, Barry Hock, Troy L Merry, Abel D Ang, Bridget A Robinson, Margaret J Currie, Gabi U Dachs
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Publicado: Public Library of Science (PLoS) 2021
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spelling oai:doaj.org-article:660dd8995a24455fb304ef382e12afa92021-12-02T20:16:47ZEffect of immune modulation on the skeletal muscle mitochondrial exercise response: An exploratory study in mice with cancer.1932-620310.1371/journal.pone.0258831https://doaj.org/article/660dd8995a24455fb304ef382e12afa92021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258831https://doaj.org/toc/1932-6203Cancer 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.Linda A BussBarry HockTroy L MerryAbel D AngBridget A RobinsonMargaret J CurrieGabi U DachsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0258831 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Linda A Buss
Barry Hock
Troy L Merry
Abel D Ang
Bridget A Robinson
Margaret J Currie
Gabi U Dachs
Effect of immune modulation on the skeletal muscle mitochondrial exercise response: An exploratory study in mice with cancer.
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.
format article
author Linda A Buss
Barry Hock
Troy L Merry
Abel D Ang
Bridget A Robinson
Margaret J Currie
Gabi U Dachs
author_facet Linda A Buss
Barry Hock
Troy L Merry
Abel D Ang
Bridget A Robinson
Margaret J Currie
Gabi U Dachs
author_sort Linda A Buss
title 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_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_sort effect of immune modulation on the skeletal muscle mitochondrial exercise response: an exploratory study in mice with cancer.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/660dd8995a24455fb304ef382e12afa9
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