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PD-L1(ATTAC) mice reveal the potential of depleting PD-L1 expressing cells in cancer therapy
Antibodies targeting the PD-1 receptor and its ligand PD-L1 have shown impressive responses in some tumors of bad prognosis. We hypothesized that, since immunosuppressive cells might present several immune checkpoints on their surface, the selective elimination of PD-L1 expressing cells could be eff...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10085585/ https://www.ncbi.nlm.nih.gov/pubmed/36947705 http://dx.doi.org/10.18632/aging.204598 |
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author | Fueyo-Marcos, Elena Lopez-Pernas, Gema Fustero-Torre, Coral Antón, Marta Elena Al-Shahrour, Fátima Fernández-Capetillo, Oscar Murga, Matilde |
author_facet | Fueyo-Marcos, Elena Lopez-Pernas, Gema Fustero-Torre, Coral Antón, Marta Elena Al-Shahrour, Fátima Fernández-Capetillo, Oscar Murga, Matilde |
author_sort | Fueyo-Marcos, Elena |
collection | PubMed |
description | Antibodies targeting the PD-1 receptor and its ligand PD-L1 have shown impressive responses in some tumors of bad prognosis. We hypothesized that, since immunosuppressive cells might present several immune checkpoints on their surface, the selective elimination of PD-L1 expressing cells could be efficacious in enabling the activation of antitumoral immune responses. To address this question, we developed an inducible suicidal knock-in mouse allele of Pd-l1 (PD-L1(ATTAC)) which allows for the tracking and specific elimination of PD-L1-expressing cells in adult tissues. Consistent with our hypothesis, elimination of PD-L1 expressing cells from the mouse peritoneum increased the septic response to lipopolysaccharide (LPS), due to an exacerbated inflammatory response to the endotoxin. In addition, mice depleted of PD-L1(+) cells were resistant to colon cancer peritoneal allografts, which was associated with a loss of immunosuppressive B cells and macrophages, concomitant with an increase in activated cytotoxic CD8 T cells. Collectively, these results illustrate the usefulness of PD-L1(ATTAC) mice for research in immunotherapy and provide genetic support to the concept of targeting PD-L1 expressing cells in cancer. |
format | Online Article Text |
id | pubmed-10085585 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-100855852023-04-11 PD-L1(ATTAC) mice reveal the potential of depleting PD-L1 expressing cells in cancer therapy Fueyo-Marcos, Elena Lopez-Pernas, Gema Fustero-Torre, Coral Antón, Marta Elena Al-Shahrour, Fátima Fernández-Capetillo, Oscar Murga, Matilde Aging (Albany NY) Research Paper Antibodies targeting the PD-1 receptor and its ligand PD-L1 have shown impressive responses in some tumors of bad prognosis. We hypothesized that, since immunosuppressive cells might present several immune checkpoints on their surface, the selective elimination of PD-L1 expressing cells could be efficacious in enabling the activation of antitumoral immune responses. To address this question, we developed an inducible suicidal knock-in mouse allele of Pd-l1 (PD-L1(ATTAC)) which allows for the tracking and specific elimination of PD-L1-expressing cells in adult tissues. Consistent with our hypothesis, elimination of PD-L1 expressing cells from the mouse peritoneum increased the septic response to lipopolysaccharide (LPS), due to an exacerbated inflammatory response to the endotoxin. In addition, mice depleted of PD-L1(+) cells were resistant to colon cancer peritoneal allografts, which was associated with a loss of immunosuppressive B cells and macrophages, concomitant with an increase in activated cytotoxic CD8 T cells. Collectively, these results illustrate the usefulness of PD-L1(ATTAC) mice for research in immunotherapy and provide genetic support to the concept of targeting PD-L1 expressing cells in cancer. Impact Journals 2023-03-22 /pmc/articles/PMC10085585/ /pubmed/36947705 http://dx.doi.org/10.18632/aging.204598 Text en Copyright: © 2023 Fueyo-Marcos et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Fueyo-Marcos, Elena Lopez-Pernas, Gema Fustero-Torre, Coral Antón, Marta Elena Al-Shahrour, Fátima Fernández-Capetillo, Oscar Murga, Matilde PD-L1(ATTAC) mice reveal the potential of depleting PD-L1 expressing cells in cancer therapy |
title | PD-L1(ATTAC) mice reveal the potential of depleting PD-L1 expressing cells in cancer therapy |
title_full | PD-L1(ATTAC) mice reveal the potential of depleting PD-L1 expressing cells in cancer therapy |
title_fullStr | PD-L1(ATTAC) mice reveal the potential of depleting PD-L1 expressing cells in cancer therapy |
title_full_unstemmed | PD-L1(ATTAC) mice reveal the potential of depleting PD-L1 expressing cells in cancer therapy |
title_short | PD-L1(ATTAC) mice reveal the potential of depleting PD-L1 expressing cells in cancer therapy |
title_sort | pd-l1(attac) mice reveal the potential of depleting pd-l1 expressing cells in cancer therapy |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10085585/ https://www.ncbi.nlm.nih.gov/pubmed/36947705 http://dx.doi.org/10.18632/aging.204598 |
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