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The Potential Advantage of Targeting Both PD-L1/PD-L2/PD-1 and IL-10–IL-10R Pathways in Acute Myeloid Leukemia

Tumor cells promote the suppression of host anti-tumor type 1 T cell responses by various mechanisms, including the upregulation of surface inhibitory molecules such as programmed death ligand (PD-L)-1, and the production of immunosuppressive cytokines such as interleukin-10 (IL-10). There are over...

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Autores principales: Jimbu, Laura, Mesaros, Oana, Neaga, Alexandra, Nanut, Ana Maria, Tomuleasa, Ciprian, Dima, Delia, Bocsan, Corina, Zdrenghea, Mihnea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8620891/
https://www.ncbi.nlm.nih.gov/pubmed/34832887
http://dx.doi.org/10.3390/ph14111105
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author Jimbu, Laura
Mesaros, Oana
Neaga, Alexandra
Nanut, Ana Maria
Tomuleasa, Ciprian
Dima, Delia
Bocsan, Corina
Zdrenghea, Mihnea
author_facet Jimbu, Laura
Mesaros, Oana
Neaga, Alexandra
Nanut, Ana Maria
Tomuleasa, Ciprian
Dima, Delia
Bocsan, Corina
Zdrenghea, Mihnea
author_sort Jimbu, Laura
collection PubMed
description Tumor cells promote the suppression of host anti-tumor type 1 T cell responses by various mechanisms, including the upregulation of surface inhibitory molecules such as programmed death ligand (PD-L)-1, and the production of immunosuppressive cytokines such as interleukin-10 (IL-10). There are over 2000 trials investigating PD-L1 and/or its receptor programmed-death 1 (PD-1) blockade in cancer, leading to the approval of PD-1 or PD-L1 inhibitors in several types of solid cancers and in hematological malignancies. The available data suggest that the molecule PD-L1 on antigen-presenting cells suppresses type 1 T cell immune responses such as cytotoxicity, and that the cytokine IL-10, in addition to downregulating immune responses, increases the expression of inhibitory molecule PD-L1. We hypothesize that the manipulation of both the co-inhibitory network (with anti-PD-L1 blocking antibodies) and suppressor network (with anti-IL-10 blocking antibodies) is an attractive immunotherapeutic intervention for acute myeloid leukemia (AML) patients ineligible for standard treatment with chemotherapy and hematopoietic stem cell transplantation, and with less severe adverse reactions. The proposed combination of these two immunotherapies represents a new approach that can be readily translated into the clinic to improve the therapeutic efficacy of AML disease treatment.
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spelling pubmed-86208912021-11-27 The Potential Advantage of Targeting Both PD-L1/PD-L2/PD-1 and IL-10–IL-10R Pathways in Acute Myeloid Leukemia Jimbu, Laura Mesaros, Oana Neaga, Alexandra Nanut, Ana Maria Tomuleasa, Ciprian Dima, Delia Bocsan, Corina Zdrenghea, Mihnea Pharmaceuticals (Basel) Review Tumor cells promote the suppression of host anti-tumor type 1 T cell responses by various mechanisms, including the upregulation of surface inhibitory molecules such as programmed death ligand (PD-L)-1, and the production of immunosuppressive cytokines such as interleukin-10 (IL-10). There are over 2000 trials investigating PD-L1 and/or its receptor programmed-death 1 (PD-1) blockade in cancer, leading to the approval of PD-1 or PD-L1 inhibitors in several types of solid cancers and in hematological malignancies. The available data suggest that the molecule PD-L1 on antigen-presenting cells suppresses type 1 T cell immune responses such as cytotoxicity, and that the cytokine IL-10, in addition to downregulating immune responses, increases the expression of inhibitory molecule PD-L1. We hypothesize that the manipulation of both the co-inhibitory network (with anti-PD-L1 blocking antibodies) and suppressor network (with anti-IL-10 blocking antibodies) is an attractive immunotherapeutic intervention for acute myeloid leukemia (AML) patients ineligible for standard treatment with chemotherapy and hematopoietic stem cell transplantation, and with less severe adverse reactions. The proposed combination of these two immunotherapies represents a new approach that can be readily translated into the clinic to improve the therapeutic efficacy of AML disease treatment. MDPI 2021-10-29 /pmc/articles/PMC8620891/ /pubmed/34832887 http://dx.doi.org/10.3390/ph14111105 Text en © 2021 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 Review
Jimbu, Laura
Mesaros, Oana
Neaga, Alexandra
Nanut, Ana Maria
Tomuleasa, Ciprian
Dima, Delia
Bocsan, Corina
Zdrenghea, Mihnea
The Potential Advantage of Targeting Both PD-L1/PD-L2/PD-1 and IL-10–IL-10R Pathways in Acute Myeloid Leukemia
title The Potential Advantage of Targeting Both PD-L1/PD-L2/PD-1 and IL-10–IL-10R Pathways in Acute Myeloid Leukemia
title_full The Potential Advantage of Targeting Both PD-L1/PD-L2/PD-1 and IL-10–IL-10R Pathways in Acute Myeloid Leukemia
title_fullStr The Potential Advantage of Targeting Both PD-L1/PD-L2/PD-1 and IL-10–IL-10R Pathways in Acute Myeloid Leukemia
title_full_unstemmed The Potential Advantage of Targeting Both PD-L1/PD-L2/PD-1 and IL-10–IL-10R Pathways in Acute Myeloid Leukemia
title_short The Potential Advantage of Targeting Both PD-L1/PD-L2/PD-1 and IL-10–IL-10R Pathways in Acute Myeloid Leukemia
title_sort potential advantage of targeting both pd-l1/pd-l2/pd-1 and il-10–il-10r pathways in acute myeloid leukemia
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8620891/
https://www.ncbi.nlm.nih.gov/pubmed/34832887
http://dx.doi.org/10.3390/ph14111105
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