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Nigericin Boosts Anti-Tumor Immune Response via Inducing Pyroptosis in Triple-Negative Breast Cancer

SIMPLE SUMMARY: The response rate of advanced triple-negative breast cancer (TNBC) to immune checkpoint inhibitors remains unsatisfactory. Recent studies showed that inducing pyroptosis in tumor cells can amplify the anti-tumor immune response by turning “cold” tumors into “hot” tumors. Here, we dem...

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Autores principales: Wu, Lisha, Bai, Shoumin, Huang, Jing, Cui, Guohui, Li, Qingjian, Wang, Jingshu, Du, Xin, Fu, Wenkui, Li, Chuping, Wei, Wei, Lin, Huan, Luo, Man-Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10296105/
https://www.ncbi.nlm.nih.gov/pubmed/37370831
http://dx.doi.org/10.3390/cancers15123221
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author Wu, Lisha
Bai, Shoumin
Huang, Jing
Cui, Guohui
Li, Qingjian
Wang, Jingshu
Du, Xin
Fu, Wenkui
Li, Chuping
Wei, Wei
Lin, Huan
Luo, Man-Li
author_facet Wu, Lisha
Bai, Shoumin
Huang, Jing
Cui, Guohui
Li, Qingjian
Wang, Jingshu
Du, Xin
Fu, Wenkui
Li, Chuping
Wei, Wei
Lin, Huan
Luo, Man-Li
author_sort Wu, Lisha
collection PubMed
description SIMPLE SUMMARY: The response rate of advanced triple-negative breast cancer (TNBC) to immune checkpoint inhibitors remains unsatisfactory. Recent studies showed that inducing pyroptosis in tumor cells can amplify the anti-tumor immune response by turning “cold” tumors into “hot” tumors. Here, we demonstrated that the antibiotic nigericin caused TNBC cell death by inducing concurrent Caspase-1/GSDMD-mediated pyroptosis and Caspase-3-mediated apoptosis. Notably, we found that nigericin-induced pyroptosis promoted the infiltration and activation of T cells, as well as showing a synergistic therapeutic effect when combined with anti-PD-1 antibody treatment. This study provides a potential strategy to utilize nigericin to boost the anti-tumor immune responses required to treat advanced TNBC. ABSTRACT: Although immune checkpoint inhibitors improved the clinical outcomes of advanced triple negative breast cancer (TBNC) patients, the response rate remains relatively low. Nigericin is an antibiotic derived from Streptomyces hydrophobicus. We found that nigericin caused cell death in TNBC cell lines MDA-MB-231 and 4T1 by inducing concurrent pyroptosis and apoptosis. As nigericin facilitated cellular potassium efflux, we discovered that it caused mitochondrial dysfunction, leading to mitochondrial ROS production, as well as activation of Caspase-1/GSDMD-mediated pyroptosis and Caspase-3-mediated apoptosis in TNBC cells. Notably, nigericin-induced pyroptosis could amplify the anti-tumor immune response by enhancing the infiltration and anti-tumor effect of CD4+ and CD8+ T cells. Moreover, nigericin showed a synergistic therapeutic effect when combined with anti-PD-1 antibody in TNBC treatment. Our study reveals that nigericin may be a promising anti-tumor agent, especially in combination with immune checkpoint inhibitors for advanced TNBC treatment.
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spelling pubmed-102961052023-06-28 Nigericin Boosts Anti-Tumor Immune Response via Inducing Pyroptosis in Triple-Negative Breast Cancer Wu, Lisha Bai, Shoumin Huang, Jing Cui, Guohui Li, Qingjian Wang, Jingshu Du, Xin Fu, Wenkui Li, Chuping Wei, Wei Lin, Huan Luo, Man-Li Cancers (Basel) Article SIMPLE SUMMARY: The response rate of advanced triple-negative breast cancer (TNBC) to immune checkpoint inhibitors remains unsatisfactory. Recent studies showed that inducing pyroptosis in tumor cells can amplify the anti-tumor immune response by turning “cold” tumors into “hot” tumors. Here, we demonstrated that the antibiotic nigericin caused TNBC cell death by inducing concurrent Caspase-1/GSDMD-mediated pyroptosis and Caspase-3-mediated apoptosis. Notably, we found that nigericin-induced pyroptosis promoted the infiltration and activation of T cells, as well as showing a synergistic therapeutic effect when combined with anti-PD-1 antibody treatment. This study provides a potential strategy to utilize nigericin to boost the anti-tumor immune responses required to treat advanced TNBC. ABSTRACT: Although immune checkpoint inhibitors improved the clinical outcomes of advanced triple negative breast cancer (TBNC) patients, the response rate remains relatively low. Nigericin is an antibiotic derived from Streptomyces hydrophobicus. We found that nigericin caused cell death in TNBC cell lines MDA-MB-231 and 4T1 by inducing concurrent pyroptosis and apoptosis. As nigericin facilitated cellular potassium efflux, we discovered that it caused mitochondrial dysfunction, leading to mitochondrial ROS production, as well as activation of Caspase-1/GSDMD-mediated pyroptosis and Caspase-3-mediated apoptosis in TNBC cells. Notably, nigericin-induced pyroptosis could amplify the anti-tumor immune response by enhancing the infiltration and anti-tumor effect of CD4+ and CD8+ T cells. Moreover, nigericin showed a synergistic therapeutic effect when combined with anti-PD-1 antibody in TNBC treatment. Our study reveals that nigericin may be a promising anti-tumor agent, especially in combination with immune checkpoint inhibitors for advanced TNBC treatment. MDPI 2023-06-16 /pmc/articles/PMC10296105/ /pubmed/37370831 http://dx.doi.org/10.3390/cancers15123221 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wu, Lisha
Bai, Shoumin
Huang, Jing
Cui, Guohui
Li, Qingjian
Wang, Jingshu
Du, Xin
Fu, Wenkui
Li, Chuping
Wei, Wei
Lin, Huan
Luo, Man-Li
Nigericin Boosts Anti-Tumor Immune Response via Inducing Pyroptosis in Triple-Negative Breast Cancer
title Nigericin Boosts Anti-Tumor Immune Response via Inducing Pyroptosis in Triple-Negative Breast Cancer
title_full Nigericin Boosts Anti-Tumor Immune Response via Inducing Pyroptosis in Triple-Negative Breast Cancer
title_fullStr Nigericin Boosts Anti-Tumor Immune Response via Inducing Pyroptosis in Triple-Negative Breast Cancer
title_full_unstemmed Nigericin Boosts Anti-Tumor Immune Response via Inducing Pyroptosis in Triple-Negative Breast Cancer
title_short Nigericin Boosts Anti-Tumor Immune Response via Inducing Pyroptosis in Triple-Negative Breast Cancer
title_sort nigericin boosts anti-tumor immune response via inducing pyroptosis in triple-negative breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10296105/
https://www.ncbi.nlm.nih.gov/pubmed/37370831
http://dx.doi.org/10.3390/cancers15123221
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