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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| Format: | Article |
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MDPI AG
2021-10-01
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| Online Access: | https://www.mdpi.com/1424-8247/14/11/1105 |
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| author | Laura Jimbu Oana Mesaros Alexandra Neaga Ana Maria Nanut Ciprian Tomuleasa Delia Dima Corina Bocsan Mihnea Zdrenghea |
| author_facet | Laura Jimbu Oana Mesaros Alexandra Neaga Ana Maria Nanut Ciprian Tomuleasa Delia Dima Corina Bocsan Mihnea Zdrenghea |
| author_sort | Laura Jimbu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:09:45Z |
| format | Article |
| id | doaj.art-30fd7aa677ee4ac38f6d8cd9ed008ba7 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T05:09:45Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-30fd7aa677ee4ac38f6d8cd9ed008ba72023-11-23T00:55:18ZengMDPI AGPharmaceuticals1424-82472021-10-011411110510.3390/ph14111105The Potential Advantage of Targeting Both PD-L1/PD-L2/PD-1 and IL-10–IL-10R Pathways in Acute Myeloid LeukemiaLaura Jimbu0Oana Mesaros1Alexandra Neaga2Ana Maria Nanut3Ciprian Tomuleasa4Delia Dima5Corina Bocsan6Mihnea Zdrenghea7Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, 8 Babes Str., 400012 Cluj-Napoca, RomaniaDepartment of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, 8 Babes Str., 400012 Cluj-Napoca, RomaniaDepartment of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, 8 Babes Str., 400012 Cluj-Napoca, RomaniaDepartment of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, 8 Babes Str., 400012 Cluj-Napoca, RomaniaDepartment of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, 8 Babes Str., 400012 Cluj-Napoca, RomaniaDepartment of Hematology, Ion Chiricuta Oncology Institute, 34-36 Republicii Str., 400015 Cluj-Napoca, RomaniaDepartment of Clinical Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, 8 Babes Str., 400012 Cluj-Napoca, RomaniaDepartment of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, 8 Babes Str., 400012 Cluj-Napoca, RomaniaTumor 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.https://www.mdpi.com/1424-8247/14/11/1105PD-1PD-L1IL-10acute myeloid leukemiacancer |
| spellingShingle | Laura Jimbu Oana Mesaros Alexandra Neaga Ana Maria Nanut Ciprian Tomuleasa Delia Dima Corina Bocsan Mihnea Zdrenghea The Potential Advantage of Targeting Both PD-L1/PD-L2/PD-1 and IL-10–IL-10R Pathways in Acute Myeloid Leukemia Pharmaceuticals PD-1 PD-L1 IL-10 acute myeloid leukemia cancer |
| 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 | PD-1 PD-L1 IL-10 acute myeloid leukemia cancer |
| url | https://www.mdpi.com/1424-8247/14/11/1105 |
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