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Immunomodulatory Effect of Proteasome Inhibitors via the Induction of Immunogenic Cell Death in Myeloma Cells

Several anti-cancer drugs are known to have immunomodulatory effects, including immunogenic cell death (ICD) of cancer cells. ICD is a form of apoptosis which is caused by the release of damage-associated molecular patterns (DAMPs), the uptake of cancer antigens by dendritic cells, and the activatio...

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Autores principales: Matsushita, Maiko, Kashiwazaki, Sho, Kamiko, Satoshi, Kobori, Michio, Osada, Makoto, Kunieda, Hisako, Hirao, Maki, Ichikawa, Daiju, Hattori, Yutaka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10609901/
https://www.ncbi.nlm.nih.gov/pubmed/37895838
http://dx.doi.org/10.3390/ph16101367
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author Matsushita, Maiko
Kashiwazaki, Sho
Kamiko, Satoshi
Kobori, Michio
Osada, Makoto
Kunieda, Hisako
Hirao, Maki
Ichikawa, Daiju
Hattori, Yutaka
author_facet Matsushita, Maiko
Kashiwazaki, Sho
Kamiko, Satoshi
Kobori, Michio
Osada, Makoto
Kunieda, Hisako
Hirao, Maki
Ichikawa, Daiju
Hattori, Yutaka
author_sort Matsushita, Maiko
collection PubMed
description Several anti-cancer drugs are known to have immunomodulatory effects, including immunogenic cell death (ICD) of cancer cells. ICD is a form of apoptosis which is caused by the release of damage-associated molecular patterns (DAMPs), the uptake of cancer antigens by dendritic cells, and the activation of acquired immunity against cancer cells. ICD was originally reported in solid tumors, and there have been few reports on ICD in multiple myeloma (MM). Here, we showed that proteasome inhibitors, including carfilzomib, induce ICD in myeloma cells via an unfolded protein response pathway distinct from that in solid tumors. Additionally, we demonstrated the potential impact of ICD on the survival of patients with myeloma. ICD induced by proteasome inhibitors is expected to improve the prognosis of MM patients not only by its cytotoxic effects, but also by building strong immune memory response against MM cells in combination with other therapies, such as chimeric antigen receptor—T cell therapy.
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spelling pubmed-106099012023-10-28 Immunomodulatory Effect of Proteasome Inhibitors via the Induction of Immunogenic Cell Death in Myeloma Cells Matsushita, Maiko Kashiwazaki, Sho Kamiko, Satoshi Kobori, Michio Osada, Makoto Kunieda, Hisako Hirao, Maki Ichikawa, Daiju Hattori, Yutaka Pharmaceuticals (Basel) Article Several anti-cancer drugs are known to have immunomodulatory effects, including immunogenic cell death (ICD) of cancer cells. ICD is a form of apoptosis which is caused by the release of damage-associated molecular patterns (DAMPs), the uptake of cancer antigens by dendritic cells, and the activation of acquired immunity against cancer cells. ICD was originally reported in solid tumors, and there have been few reports on ICD in multiple myeloma (MM). Here, we showed that proteasome inhibitors, including carfilzomib, induce ICD in myeloma cells via an unfolded protein response pathway distinct from that in solid tumors. Additionally, we demonstrated the potential impact of ICD on the survival of patients with myeloma. ICD induced by proteasome inhibitors is expected to improve the prognosis of MM patients not only by its cytotoxic effects, but also by building strong immune memory response against MM cells in combination with other therapies, such as chimeric antigen receptor—T cell therapy. MDPI 2023-09-27 /pmc/articles/PMC10609901/ /pubmed/37895838 http://dx.doi.org/10.3390/ph16101367 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
Matsushita, Maiko
Kashiwazaki, Sho
Kamiko, Satoshi
Kobori, Michio
Osada, Makoto
Kunieda, Hisako
Hirao, Maki
Ichikawa, Daiju
Hattori, Yutaka
Immunomodulatory Effect of Proteasome Inhibitors via the Induction of Immunogenic Cell Death in Myeloma Cells
title Immunomodulatory Effect of Proteasome Inhibitors via the Induction of Immunogenic Cell Death in Myeloma Cells
title_full Immunomodulatory Effect of Proteasome Inhibitors via the Induction of Immunogenic Cell Death in Myeloma Cells
title_fullStr Immunomodulatory Effect of Proteasome Inhibitors via the Induction of Immunogenic Cell Death in Myeloma Cells
title_full_unstemmed Immunomodulatory Effect of Proteasome Inhibitors via the Induction of Immunogenic Cell Death in Myeloma Cells
title_short Immunomodulatory Effect of Proteasome Inhibitors via the Induction of Immunogenic Cell Death in Myeloma Cells
title_sort immunomodulatory effect of proteasome inhibitors via the induction of immunogenic cell death in myeloma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10609901/
https://www.ncbi.nlm.nih.gov/pubmed/37895838
http://dx.doi.org/10.3390/ph16101367
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