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Combination of Cisplatin and Irradiation Induces Immunogenic Cell Death and Potentiates Postirradiation Anti–PD-1 Treatment Efficacy in Urothelial Carcinoma
The therapeutic benefit of immune checkpoint inhibitor monotherapy is limited to a subset of patients in urothelial carcinoma (UC). Previous studies showed the immunogenicity of cisplatin and irradiation. Here, we investigated whether chemoradiotherapy (CRT), a combination of cisplatin and irradiati...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825793/ https://www.ncbi.nlm.nih.gov/pubmed/33430352 http://dx.doi.org/10.3390/ijms22020535 |
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author | Fukushima, Hiroshi Yoshida, Soichiro Kijima, Toshiki Nakamura, Yuki Fukuda, Shohei Uehara, Sho Yasuda, Yosuke Tanaka, Hajime Yokoyama, Minato Matsuoka, Yoh Fujii, Yasuhisa |
author_facet | Fukushima, Hiroshi Yoshida, Soichiro Kijima, Toshiki Nakamura, Yuki Fukuda, Shohei Uehara, Sho Yasuda, Yosuke Tanaka, Hajime Yokoyama, Minato Matsuoka, Yoh Fujii, Yasuhisa |
author_sort | Fukushima, Hiroshi |
collection | PubMed |
description | The therapeutic benefit of immune checkpoint inhibitor monotherapy is limited to a subset of patients in urothelial carcinoma (UC). Previous studies showed the immunogenicity of cisplatin and irradiation. Here, we investigated whether chemoradiotherapy (CRT), a combination of cisplatin and irradiation, could improve the efficacy of postirradiation anti–programmed cell death 1 (PD-1) treatment in UC. In our advanced UC patient cohort, patients with CRT showed a significantly better objective response rate (75%/22%) and overall survival (88%/30% at 12 months) following later pembrolizumab therapy compared to those without. Then, we created syngeneic UC mouse models by inoculating MB49 cells s.c. in C57BL/6J mice to examine the potential of CRT to enhance antitumor immunity in conjunction with postirradiation anti–PD-1 treatment. Nonirradiated tumors of the mice treated with CRT/postirradiation anti–PD-1 treatment had a significantly slower growth rate and a significantly higher expression of cytotoxic T cells compared to those of the mice treated with anti–PD-1 treatment alone. The mice treated with CRT/postirradiation anti–PD-1 treatment showed the best survival. Mechanistically, CRT provoked strong direct cytotoxicity and increased expressions of immunogenic cell death markers in MB49 cells. Therefore, the combination of cisplatin and irradiation induces immunogenic cell death and potentiates postirradiation anti–PD-1 treatment efficacy in UC. |
format | Online Article Text |
id | pubmed-7825793 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-78257932021-01-24 Combination of Cisplatin and Irradiation Induces Immunogenic Cell Death and Potentiates Postirradiation Anti–PD-1 Treatment Efficacy in Urothelial Carcinoma Fukushima, Hiroshi Yoshida, Soichiro Kijima, Toshiki Nakamura, Yuki Fukuda, Shohei Uehara, Sho Yasuda, Yosuke Tanaka, Hajime Yokoyama, Minato Matsuoka, Yoh Fujii, Yasuhisa Int J Mol Sci Article The therapeutic benefit of immune checkpoint inhibitor monotherapy is limited to a subset of patients in urothelial carcinoma (UC). Previous studies showed the immunogenicity of cisplatin and irradiation. Here, we investigated whether chemoradiotherapy (CRT), a combination of cisplatin and irradiation, could improve the efficacy of postirradiation anti–programmed cell death 1 (PD-1) treatment in UC. In our advanced UC patient cohort, patients with CRT showed a significantly better objective response rate (75%/22%) and overall survival (88%/30% at 12 months) following later pembrolizumab therapy compared to those without. Then, we created syngeneic UC mouse models by inoculating MB49 cells s.c. in C57BL/6J mice to examine the potential of CRT to enhance antitumor immunity in conjunction with postirradiation anti–PD-1 treatment. Nonirradiated tumors of the mice treated with CRT/postirradiation anti–PD-1 treatment had a significantly slower growth rate and a significantly higher expression of cytotoxic T cells compared to those of the mice treated with anti–PD-1 treatment alone. The mice treated with CRT/postirradiation anti–PD-1 treatment showed the best survival. Mechanistically, CRT provoked strong direct cytotoxicity and increased expressions of immunogenic cell death markers in MB49 cells. Therefore, the combination of cisplatin and irradiation induces immunogenic cell death and potentiates postirradiation anti–PD-1 treatment efficacy in UC. MDPI 2021-01-07 /pmc/articles/PMC7825793/ /pubmed/33430352 http://dx.doi.org/10.3390/ijms22020535 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Fukushima, Hiroshi Yoshida, Soichiro Kijima, Toshiki Nakamura, Yuki Fukuda, Shohei Uehara, Sho Yasuda, Yosuke Tanaka, Hajime Yokoyama, Minato Matsuoka, Yoh Fujii, Yasuhisa Combination of Cisplatin and Irradiation Induces Immunogenic Cell Death and Potentiates Postirradiation Anti–PD-1 Treatment Efficacy in Urothelial Carcinoma |
title | Combination of Cisplatin and Irradiation Induces Immunogenic Cell Death and Potentiates Postirradiation Anti–PD-1 Treatment Efficacy in Urothelial Carcinoma |
title_full | Combination of Cisplatin and Irradiation Induces Immunogenic Cell Death and Potentiates Postirradiation Anti–PD-1 Treatment Efficacy in Urothelial Carcinoma |
title_fullStr | Combination of Cisplatin and Irradiation Induces Immunogenic Cell Death and Potentiates Postirradiation Anti–PD-1 Treatment Efficacy in Urothelial Carcinoma |
title_full_unstemmed | Combination of Cisplatin and Irradiation Induces Immunogenic Cell Death and Potentiates Postirradiation Anti–PD-1 Treatment Efficacy in Urothelial Carcinoma |
title_short | Combination of Cisplatin and Irradiation Induces Immunogenic Cell Death and Potentiates Postirradiation Anti–PD-1 Treatment Efficacy in Urothelial Carcinoma |
title_sort | combination of cisplatin and irradiation induces immunogenic cell death and potentiates postirradiation anti–pd-1 treatment efficacy in urothelial carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825793/ https://www.ncbi.nlm.nih.gov/pubmed/33430352 http://dx.doi.org/10.3390/ijms22020535 |
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