Benefits of exercise and immunotherapy in a murine model of human non-small-cell lung carcinoma

Background: Lung cancer has the highest incidence and mortality rate in the world. One of the most promising new cancer therapies in recent years is immunotherapy, which is based on the blockade of immune checkpoints such as programmed cell death protein 1 (PD-1). Exercise training is beneficial to...

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Authors: Martín Ruiz, Asunción, Fiuza Luces, María del Carmen, Rincón Castanedo, Cecilia, Fernández Moreno, David, González Gálvez, Beatriz, Martínez Martínez, Esther, Martín Acosta, Paloma, Coronado, María José, Franco Luzón, Lidia, Lucía Mulas, Alejandro, Et al.
Format: article
Publication Date:2020
Country:España
Institution:Universidad Europea (UEM)
Repository:ABACUS. Repositorio de Producción Científica
Language:English
OAI Identifier:oai:abacus.universidadeuropea.com:11268/9517
Online Access:http://hdl.handle.net/11268/9517
Access Level:Open access
Keyword:Cáncer
Inmunoterapia
Medicina deportiva
Inmunología
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spelling Benefits of exercise and immunotherapy in a murine model of human non-small-cell lung carcinomaMartín Ruiz, AsunciónFiuza Luces, María del CarmenRincón Castanedo, CeciliaFernández Moreno, DavidGonzález Gálvez, BeatrizMartínez Martínez, EstherMartín Acosta, PalomaCoronado, María JoséFranco Luzón, LidiaLucía Mulas, AlejandroEt al.CáncerInmunoterapiaMedicina deportivaCáncerInmunologíaMedicina deportivaBackground: Lung cancer has the highest incidence and mortality rate in the world. One of the most promising new cancer therapies in recent years is immunotherapy, which is based on the blockade of immune checkpoints such as programmed cell death protein 1 (PD-1). Exercise training is beneficial to maintain and improve the quality of life of cancer patients, and it might also modulate the anti-tumoral efficiency of some chemotherapeutic agents. However, the potential of exercise combined with immunotherapy as a cancer therapy remains to be elucidated. Here, we examined the effects of exercise on tumor growth and its possible adjuvant effects when combined with anti-PD-1 immunotherapy (nivolumab) in a patient derived xenograft (PDX) model of non-small-cell lung carcinoma (NSCLC). Methods: We generated a PDX model using NOD-SCID gamma mice with subcutaneous grafts from tumor tissue of a patient with NSCLC. Animals were randomly assigned to one of four groups: non-exercise + isotype control (n=5), exercise + isotype control (n=5), non-exercise + nivolumab (n=6) or exercise + nivolumab (n=6). The animals undertook an 8- week moderate-intensity training regimen (treadmill aerobic exercise and strength training). Immunotherapy (nivolumab) or an isotype control was administered 2 days/week, for 6 weeks. Several tumor growth and microenvironment parameters were measured after the intervention. Results: Improvements in aerobic capacity and muscle strength (p=0.027 and p=0.005) were noted in exercised animals. Exercise alone reduced the tumor growth rate with respect to non-exercised mice (p=0.050). The double intervention (exercise + nivolumab) increased tumor necrosis and reduced apoptosis with respect to controls (p=0.026; p=0.030). All interventions achieved a reduction in proliferation compared with the control group (p=0.015, p=0.011, and p=0.011). Exercise alone increased myeloid tumor infiltrates (mostly neutrophils) with respect to the nivolumab only group (p=0.018). Finally, Vegf-a expression was higher in the nivolumab groups (in combination or not with exercise) than in exercise + isotype control group (p=0.045 and p=0.047, respectively). No other significant effects were found. Conclusions: Our results would suggest that aerobic and strength training should be studied as an adjuvant to cancer immunotherapy treatment.20202020-11-2120202020-01-0120202020-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articlehttp://hdl.handle.net/11268/9517reponame:ABACUS. Repositorio de Producción Científicainstname:Universidad Europea (UEM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:abacus.universidadeuropea.com:11268/95172026-06-11T12:41:27Z
dc.title.none.fl_str_mv Benefits of exercise and immunotherapy in a murine model of human non-small-cell lung carcinoma
title Benefits of exercise and immunotherapy in a murine model of human non-small-cell lung carcinoma
spellingShingle Benefits of exercise and immunotherapy in a murine model of human non-small-cell lung carcinoma
Martín Ruiz, Asunción
Cáncer
Inmunoterapia
Medicina deportiva
Cáncer
Inmunología
Medicina deportiva
title_short Benefits of exercise and immunotherapy in a murine model of human non-small-cell lung carcinoma
title_full Benefits of exercise and immunotherapy in a murine model of human non-small-cell lung carcinoma
title_fullStr Benefits of exercise and immunotherapy in a murine model of human non-small-cell lung carcinoma
title_full_unstemmed Benefits of exercise and immunotherapy in a murine model of human non-small-cell lung carcinoma
title_sort Benefits of exercise and immunotherapy in a murine model of human non-small-cell lung carcinoma
dc.creator.none.fl_str_mv Martín Ruiz, Asunción
Fiuza Luces, María del Carmen
Rincón Castanedo, Cecilia
Fernández Moreno, David
González Gálvez, Beatriz
Martínez Martínez, Esther
Martín Acosta, Paloma
Coronado, María José
Franco Luzón, Lidia
Lucía Mulas, Alejandro
Et al.
author Martín Ruiz, Asunción
author_facet Martín Ruiz, Asunción
Fiuza Luces, María del Carmen
Rincón Castanedo, Cecilia
Fernández Moreno, David
González Gálvez, Beatriz
Martínez Martínez, Esther
Martín Acosta, Paloma
Coronado, María José
Franco Luzón, Lidia
Lucía Mulas, Alejandro
Et al.
author_role author
author2 Fiuza Luces, María del Carmen
Rincón Castanedo, Cecilia
Fernández Moreno, David
González Gálvez, Beatriz
Martínez Martínez, Esther
Martín Acosta, Paloma
Coronado, María José
Franco Luzón, Lidia
Lucía Mulas, Alejandro
Et al.
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Cáncer
Inmunoterapia
Medicina deportiva
Cáncer
Inmunología
Medicina deportiva
topic Cáncer
Inmunoterapia
Medicina deportiva
Cáncer
Inmunología
Medicina deportiva
description Background: Lung cancer has the highest incidence and mortality rate in the world. One of the most promising new cancer therapies in recent years is immunotherapy, which is based on the blockade of immune checkpoints such as programmed cell death protein 1 (PD-1). Exercise training is beneficial to maintain and improve the quality of life of cancer patients, and it might also modulate the anti-tumoral efficiency of some chemotherapeutic agents. However, the potential of exercise combined with immunotherapy as a cancer therapy remains to be elucidated. Here, we examined the effects of exercise on tumor growth and its possible adjuvant effects when combined with anti-PD-1 immunotherapy (nivolumab) in a patient derived xenograft (PDX) model of non-small-cell lung carcinoma (NSCLC). Methods: We generated a PDX model using NOD-SCID gamma mice with subcutaneous grafts from tumor tissue of a patient with NSCLC. Animals were randomly assigned to one of four groups: non-exercise + isotype control (n=5), exercise + isotype control (n=5), non-exercise + nivolumab (n=6) or exercise + nivolumab (n=6). The animals undertook an 8- week moderate-intensity training regimen (treadmill aerobic exercise and strength training). Immunotherapy (nivolumab) or an isotype control was administered 2 days/week, for 6 weeks. Several tumor growth and microenvironment parameters were measured after the intervention. Results: Improvements in aerobic capacity and muscle strength (p=0.027 and p=0.005) were noted in exercised animals. Exercise alone reduced the tumor growth rate with respect to non-exercised mice (p=0.050). The double intervention (exercise + nivolumab) increased tumor necrosis and reduced apoptosis with respect to controls (p=0.026; p=0.030). All interventions achieved a reduction in proliferation compared with the control group (p=0.015, p=0.011, and p=0.011). Exercise alone increased myeloid tumor infiltrates (mostly neutrophils) with respect to the nivolumab only group (p=0.018). Finally, Vegf-a expression was higher in the nivolumab groups (in combination or not with exercise) than in exercise + isotype control group (p=0.045 and p=0.047, respectively). No other significant effects were found. Conclusions: Our results would suggest that aerobic and strength training should be studied as an adjuvant to cancer immunotherapy treatment.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-11-21
2020
2020-01-01
2020
2020-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/11268/9517
url http://hdl.handle.net/11268/9517
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:ABACUS. Repositorio de Producción Científica
instname:Universidad Europea (UEM)
instname_str Universidad Europea (UEM)
reponame_str ABACUS. Repositorio de Producción Científica
collection ABACUS. Repositorio de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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