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PD-1 blockade synergizes with oxaliplatin-based, but not cisplatin-based, chemotherapy of gastric cancer
Preclinical experimentation revealed that established cancers treated with the immunogenic cell death (ICD) inducer oxaliplatin are sensitized to immune checkpoint inhibitors targeting PD-1. In contrast, no such sensitizing effect is observed when cisplatin, a non-immunogenic cell death inducer is u...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235886/ https://www.ncbi.nlm.nih.gov/pubmed/35769948 http://dx.doi.org/10.1080/2162402X.2022.2093518 |
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author | Liu, Peng Chen, Jianzhou Zhao, Liwei Hollebecque, Antoine Kepp, Oliver Zitvogel, Laurence Kroemer, Guido |
author_facet | Liu, Peng Chen, Jianzhou Zhao, Liwei Hollebecque, Antoine Kepp, Oliver Zitvogel, Laurence Kroemer, Guido |
author_sort | Liu, Peng |
collection | PubMed |
description | Preclinical experimentation revealed that established cancers treated with the immunogenic cell death (ICD) inducer oxaliplatin are sensitized to immune checkpoint inhibitors targeting PD-1. In contrast, no such sensitizing effect is observed when cisplatin, a non-immunogenic cell death inducer is used. Two randomized phase III clinical trials targeting unresectable gastric and gastro-esophageal junction carcinomas apparently validate this observation. Thus, oxaliplatin-based chemotherapy (together with capecitabine or 5-fluorouracil plus leucovorin) favorably interacted with nivolumab, yielding improved outcome. In contrast, the outcome of cisplatin-based chemotherapy (together with capecitabine or 5-fluorouracil) failed to be improved by concomitant treatment with pembrolizumab. These clinical findings underscore the importance of choosing appropriate ICD-inducing cytotoxicants for the development of chemoimmunotherapeutic regimens. Unfortunately, the FDA and EMA have approved PD-1 blockade in combination with “platinum-based chemotherapy” without specifying the precise nature of the platinum-containing drug. This is a non sequitur. Based on the available clinical data, such approvals should be restricted to the use of oxaliplatin. |
format | Online Article Text |
id | pubmed-9235886 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-92358862022-06-28 PD-1 blockade synergizes with oxaliplatin-based, but not cisplatin-based, chemotherapy of gastric cancer Liu, Peng Chen, Jianzhou Zhao, Liwei Hollebecque, Antoine Kepp, Oliver Zitvogel, Laurence Kroemer, Guido Oncoimmunology Review Preclinical experimentation revealed that established cancers treated with the immunogenic cell death (ICD) inducer oxaliplatin are sensitized to immune checkpoint inhibitors targeting PD-1. In contrast, no such sensitizing effect is observed when cisplatin, a non-immunogenic cell death inducer is used. Two randomized phase III clinical trials targeting unresectable gastric and gastro-esophageal junction carcinomas apparently validate this observation. Thus, oxaliplatin-based chemotherapy (together with capecitabine or 5-fluorouracil plus leucovorin) favorably interacted with nivolumab, yielding improved outcome. In contrast, the outcome of cisplatin-based chemotherapy (together with capecitabine or 5-fluorouracil) failed to be improved by concomitant treatment with pembrolizumab. These clinical findings underscore the importance of choosing appropriate ICD-inducing cytotoxicants for the development of chemoimmunotherapeutic regimens. Unfortunately, the FDA and EMA have approved PD-1 blockade in combination with “platinum-based chemotherapy” without specifying the precise nature of the platinum-containing drug. This is a non sequitur. Based on the available clinical data, such approvals should be restricted to the use of oxaliplatin. Taylor & Francis 2022-06-24 /pmc/articles/PMC9235886/ /pubmed/35769948 http://dx.doi.org/10.1080/2162402X.2022.2093518 Text en © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Liu, Peng Chen, Jianzhou Zhao, Liwei Hollebecque, Antoine Kepp, Oliver Zitvogel, Laurence Kroemer, Guido PD-1 blockade synergizes with oxaliplatin-based, but not cisplatin-based, chemotherapy of gastric cancer |
title | PD-1 blockade synergizes with oxaliplatin-based, but not cisplatin-based, chemotherapy of gastric cancer |
title_full | PD-1 blockade synergizes with oxaliplatin-based, but not cisplatin-based, chemotherapy of gastric cancer |
title_fullStr | PD-1 blockade synergizes with oxaliplatin-based, but not cisplatin-based, chemotherapy of gastric cancer |
title_full_unstemmed | PD-1 blockade synergizes with oxaliplatin-based, but not cisplatin-based, chemotherapy of gastric cancer |
title_short | PD-1 blockade synergizes with oxaliplatin-based, but not cisplatin-based, chemotherapy of gastric cancer |
title_sort | pd-1 blockade synergizes with oxaliplatin-based, but not cisplatin-based, chemotherapy of gastric cancer |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235886/ https://www.ncbi.nlm.nih.gov/pubmed/35769948 http://dx.doi.org/10.1080/2162402X.2022.2093518 |
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