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Macrophage polarization synergizes with oxaliplatin in lung cancer immunotherapy via enhanced tumor cell phagocytosis

Calreticulin (CALR) exposure is required for most immunogenic cell death (ICD) in the anti-tumor immunity induced by chemotherapeutic agents. The present study aimed to explore the anti-tumor efficacy of the combined administration of oxaliplatin (OXA) and R848 (an agent for macrophage polarization)...

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Autores principales: Li, Fei, Zheng, Xue, Wang, Xue, Xu, Jinhua, Zhang, Qianyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365514/
https://www.ncbi.nlm.nih.gov/pubmed/34390893
http://dx.doi.org/10.1016/j.tranon.2021.101202
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author Li, Fei
Zheng, Xue
Wang, Xue
Xu, Jinhua
Zhang, Qianyun
author_facet Li, Fei
Zheng, Xue
Wang, Xue
Xu, Jinhua
Zhang, Qianyun
author_sort Li, Fei
collection PubMed
description Calreticulin (CALR) exposure is required for most immunogenic cell death (ICD) in the anti-tumor immunity induced by chemotherapeutic agents. The present study aimed to explore the anti-tumor efficacy of the combined administration of oxaliplatin (OXA) and R848 (an agent for macrophage polarization) in lung cancer cells. Flow cytometry and immunostaining assays were performed to evaluate CALR exposure induced by OXA in the murine Lewis lung carcinoma (LLC) cells. The phagocytosis of macrophages was determined using flow cytometry and western blotting assays. The anti-tumor efficacy of the OXA and R848 combination was evaluated using flow cytometry and western blotting in vitro and in vivo. OXA induced CALR exposure on the surface of LLC cells after low dose and short duration of treatment (20 μM OXA for 24 h). LLC cells pretreated with OXA were more prone to be phagocytized by M1 than M2 macrophages. M2 macrophages repolarized to M1 by R848 in vitro showed enhanced phagocytic ability to OXA-treated LLC cells. Finally, combined administration of OXA and R848 exhibited a synergistic anti-tumor effect than single agent applied in vitro and in vivo. Macrophage polarization from pro-tumor M2 to anti-tumor M1 synergizes with OXA in lung cancer immunotherapy via enhanced tumor cell phagocytosis.
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spelling pubmed-83655142021-08-23 Macrophage polarization synergizes with oxaliplatin in lung cancer immunotherapy via enhanced tumor cell phagocytosis Li, Fei Zheng, Xue Wang, Xue Xu, Jinhua Zhang, Qianyun Transl Oncol Original Research Calreticulin (CALR) exposure is required for most immunogenic cell death (ICD) in the anti-tumor immunity induced by chemotherapeutic agents. The present study aimed to explore the anti-tumor efficacy of the combined administration of oxaliplatin (OXA) and R848 (an agent for macrophage polarization) in lung cancer cells. Flow cytometry and immunostaining assays were performed to evaluate CALR exposure induced by OXA in the murine Lewis lung carcinoma (LLC) cells. The phagocytosis of macrophages was determined using flow cytometry and western blotting assays. The anti-tumor efficacy of the OXA and R848 combination was evaluated using flow cytometry and western blotting in vitro and in vivo. OXA induced CALR exposure on the surface of LLC cells after low dose and short duration of treatment (20 μM OXA for 24 h). LLC cells pretreated with OXA were more prone to be phagocytized by M1 than M2 macrophages. M2 macrophages repolarized to M1 by R848 in vitro showed enhanced phagocytic ability to OXA-treated LLC cells. Finally, combined administration of OXA and R848 exhibited a synergistic anti-tumor effect than single agent applied in vitro and in vivo. Macrophage polarization from pro-tumor M2 to anti-tumor M1 synergizes with OXA in lung cancer immunotherapy via enhanced tumor cell phagocytosis. Neoplasia Press 2021-08-12 /pmc/articles/PMC8365514/ /pubmed/34390893 http://dx.doi.org/10.1016/j.tranon.2021.101202 Text en © 2021 Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research
Li, Fei
Zheng, Xue
Wang, Xue
Xu, Jinhua
Zhang, Qianyun
Macrophage polarization synergizes with oxaliplatin in lung cancer immunotherapy via enhanced tumor cell phagocytosis
title Macrophage polarization synergizes with oxaliplatin in lung cancer immunotherapy via enhanced tumor cell phagocytosis
title_full Macrophage polarization synergizes with oxaliplatin in lung cancer immunotherapy via enhanced tumor cell phagocytosis
title_fullStr Macrophage polarization synergizes with oxaliplatin in lung cancer immunotherapy via enhanced tumor cell phagocytosis
title_full_unstemmed Macrophage polarization synergizes with oxaliplatin in lung cancer immunotherapy via enhanced tumor cell phagocytosis
title_short Macrophage polarization synergizes with oxaliplatin in lung cancer immunotherapy via enhanced tumor cell phagocytosis
title_sort macrophage polarization synergizes with oxaliplatin in lung cancer immunotherapy via enhanced tumor cell phagocytosis
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365514/
https://www.ncbi.nlm.nih.gov/pubmed/34390893
http://dx.doi.org/10.1016/j.tranon.2021.101202
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