Immunotherapy with Monoclonal Antibodies in Lung Cancer of Mice: Oxidative Stress and Other Biological Events

<i>Background:</i> Lung cancer (LC) is a major leading cause of death worldwide. Immunomodulators that target several immune mechanisms have proven to reduce tumor burden in experimental models through induction of the immune microenvironment. We hypothesized that other biological mechan...

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Main Authors: Jun Tang, Daniel Ramis-Cabrer, Xuejie Wang, Esther Barreiro
Format: Article
Language:English
Published: MDPI AG 2019-09-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/11/9/1301
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author Jun Tang
Daniel Ramis-Cabrer
Xuejie Wang
Esther Barreiro
author_facet Jun Tang
Daniel Ramis-Cabrer
Xuejie Wang
Esther Barreiro
author_sort Jun Tang
collection DOAJ
description <i>Background:</i> Lung cancer (LC) is a major leading cause of death worldwide. Immunomodulators that target several immune mechanisms have proven to reduce tumor burden in experimental models through induction of the immune microenvironment. We hypothesized that other biological mechanisms may also favor tumor burden reduction in lung cancer-bearing mice treated with immunomodulators. <i>Methods:</i> Tumor weight, area, T cells and tumor growth (immunohistochemistry), oxidative stress, apoptosis, autophagy, and signaling (NF-&#954;B and sirtuin-1) markers were analyzed (immunoblotting) in subcutaneous tumor of BALB/c mice injected with LP07 adenocarcinoma cells treated with monoclonal antibodies (CD-137, CTLA-4, PD-1, and CD-19, <i>N</i> = 9/group) and non-treated control animals. <i>Results:</i> Compared to non-treated cancer mice, in tumors of monoclonal-treated animals, tumor area and weight and ki-67 were significantly reduced, while T cell counts, oxidative stress, apoptosis, autophagy, activated p65, and sirtuin-1 markers were increased. <i>Conclusions:</i> Immunomodulators elicited a reduction in tumor burden (reduced tumor size and weight) through decreased tumor proliferation and increased oxidative stress, apoptosis, autophagy, and signaling markers, which may have interfered with the immune profile of the tumor microenvironment. Future research should be devoted to the elucidation of the specific contribution of each biological mechanism to the reduced tumor burden.
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spelling doaj.art-56d2eef0a7b148cf851cbd5eb3b249852023-09-02T23:07:29ZengMDPI AGCancers2072-66942019-09-01119130110.3390/cancers11091301cancers11091301Immunotherapy with Monoclonal Antibodies in Lung Cancer of Mice: Oxidative Stress and Other Biological EventsJun Tang0Daniel Ramis-Cabrer1Xuejie Wang2Esther Barreiro3Pulmonology Department-Muscle Wasting &amp; Cachexia in Chronic Respiratory Diseases &amp; Lung Cancer Research Group, IMIM-<i>Hospital del Mar, Parc de Salut Mar</i>, Biomedical Research Park (PRBB), C/Dr. Aiguader, 88, E-08003 Barcelona, SpainPulmonology Department-Muscle Wasting &amp; Cachexia in Chronic Respiratory Diseases &amp; Lung Cancer Research Group, IMIM-<i>Hospital del Mar, Parc de Salut Mar</i>, Biomedical Research Park (PRBB), C/Dr. Aiguader, 88, E-08003 Barcelona, SpainPulmonology Department-Muscle Wasting &amp; Cachexia in Chronic Respiratory Diseases &amp; Lung Cancer Research Group, IMIM-<i>Hospital del Mar, Parc de Salut Mar</i>, Biomedical Research Park (PRBB), C/Dr. Aiguader, 88, E-08003 Barcelona, SpainPulmonology Department-Muscle Wasting &amp; Cachexia in Chronic Respiratory Diseases &amp; Lung Cancer Research Group, IMIM-<i>Hospital del Mar, Parc de Salut Mar</i>, Biomedical Research Park (PRBB), C/Dr. Aiguader, 88, E-08003 Barcelona, Spain<i>Background:</i> Lung cancer (LC) is a major leading cause of death worldwide. Immunomodulators that target several immune mechanisms have proven to reduce tumor burden in experimental models through induction of the immune microenvironment. We hypothesized that other biological mechanisms may also favor tumor burden reduction in lung cancer-bearing mice treated with immunomodulators. <i>Methods:</i> Tumor weight, area, T cells and tumor growth (immunohistochemistry), oxidative stress, apoptosis, autophagy, and signaling (NF-&#954;B and sirtuin-1) markers were analyzed (immunoblotting) in subcutaneous tumor of BALB/c mice injected with LP07 adenocarcinoma cells treated with monoclonal antibodies (CD-137, CTLA-4, PD-1, and CD-19, <i>N</i> = 9/group) and non-treated control animals. <i>Results:</i> Compared to non-treated cancer mice, in tumors of monoclonal-treated animals, tumor area and weight and ki-67 were significantly reduced, while T cell counts, oxidative stress, apoptosis, autophagy, activated p65, and sirtuin-1 markers were increased. <i>Conclusions:</i> Immunomodulators elicited a reduction in tumor burden (reduced tumor size and weight) through decreased tumor proliferation and increased oxidative stress, apoptosis, autophagy, and signaling markers, which may have interfered with the immune profile of the tumor microenvironment. Future research should be devoted to the elucidation of the specific contribution of each biological mechanism to the reduced tumor burden.https://www.mdpi.com/2072-6694/11/9/1301experimental lung cancerimmunomodulatorsoxidative stressautophagytumor growthsirtuin-1
spellingShingle Jun Tang
Daniel Ramis-Cabrer
Xuejie Wang
Esther Barreiro
Immunotherapy with Monoclonal Antibodies in Lung Cancer of Mice: Oxidative Stress and Other Biological Events
Cancers
experimental lung cancer
immunomodulators
oxidative stress
autophagy
tumor growth
sirtuin-1
title Immunotherapy with Monoclonal Antibodies in Lung Cancer of Mice: Oxidative Stress and Other Biological Events
title_full Immunotherapy with Monoclonal Antibodies in Lung Cancer of Mice: Oxidative Stress and Other Biological Events
title_fullStr Immunotherapy with Monoclonal Antibodies in Lung Cancer of Mice: Oxidative Stress and Other Biological Events
title_full_unstemmed Immunotherapy with Monoclonal Antibodies in Lung Cancer of Mice: Oxidative Stress and Other Biological Events
title_short Immunotherapy with Monoclonal Antibodies in Lung Cancer of Mice: Oxidative Stress and Other Biological Events
title_sort immunotherapy with monoclonal antibodies in lung cancer of mice oxidative stress and other biological events
topic experimental lung cancer
immunomodulators
oxidative stress
autophagy
tumor growth
sirtuin-1
url https://www.mdpi.com/2072-6694/11/9/1301
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AT danielramiscabrer immunotherapywithmonoclonalantibodiesinlungcancerofmiceoxidativestressandotherbiologicalevents
AT xuejiewang immunotherapywithmonoclonalantibodiesinlungcancerofmiceoxidativestressandotherbiologicalevents
AT estherbarreiro immunotherapywithmonoclonalantibodiesinlungcancerofmiceoxidativestressandotherbiologicalevents