Cargando…
The role of dendritic cells for therapy of B-cell lymphoma with immune checkpoint inhibitors
Immune checkpoint blocking (ICB) is a promising new tool of cancer treatment. Yet, the underlying therapeutic mechanisms are not fully understood. Here we investigated the role of dendritic cells (DCs) for the therapeutic effect of ICB in a λ-MYC-transgenic mouse model of endogenously arising B-cell...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053142/ https://www.ncbi.nlm.nih.gov/pubmed/33141285 http://dx.doi.org/10.1007/s00262-020-02767-6 |
_version_ | 1783680061167108096 |
---|---|
author | Scheuerpflug, Anne Ahmetlić, Fatima Bauer, Vera Riedel, Tanja Röcken, Martin Mocikat, Ralph |
author_facet | Scheuerpflug, Anne Ahmetlić, Fatima Bauer, Vera Riedel, Tanja Röcken, Martin Mocikat, Ralph |
author_sort | Scheuerpflug, Anne |
collection | PubMed |
description | Immune checkpoint blocking (ICB) is a promising new tool of cancer treatment. Yet, the underlying therapeutic mechanisms are not fully understood. Here we investigated the role of dendritic cells (DCs) for the therapeutic effect of ICB in a λ-MYC-transgenic mouse model of endogenously arising B-cell lymphoma. The growth of these tumors can be effectively delayed by antibodies against CTLA-4 and PD-1. Tumor-infiltrating DCs from mice having received therapy showed an upregulation of costimulatory molecules as well as an augmented IL-12/IL-10 ratio as compared to untreated controls. Both alterations seemed to be induced by interferon-γ (IFN-γ), which is upregulated in T cells and natural killer cells upon ICB. Furthermore, the enhanced IL-12/IL-10 ratio, which favors Th1-prone antitumor T-cell responses, was a consequence of direct interaction of ICB antibodies with DCs. Importantly, the capability of tumor-infiltrating DCs of stimulating peptide-specific or allogeneic T-cell responses in vitro was improved when DCs were derived from ICB-treated mice. The data indicate that ICB therapy is not only effective by directly activating T cells, but also by triggering a complex network, in which DCs play a pivotal role at the interface between innate and adaptive antitumor responses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00262-020-02767-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-8053142 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-80531422021-04-29 The role of dendritic cells for therapy of B-cell lymphoma with immune checkpoint inhibitors Scheuerpflug, Anne Ahmetlić, Fatima Bauer, Vera Riedel, Tanja Röcken, Martin Mocikat, Ralph Cancer Immunol Immunother Original Article Immune checkpoint blocking (ICB) is a promising new tool of cancer treatment. Yet, the underlying therapeutic mechanisms are not fully understood. Here we investigated the role of dendritic cells (DCs) for the therapeutic effect of ICB in a λ-MYC-transgenic mouse model of endogenously arising B-cell lymphoma. The growth of these tumors can be effectively delayed by antibodies against CTLA-4 and PD-1. Tumor-infiltrating DCs from mice having received therapy showed an upregulation of costimulatory molecules as well as an augmented IL-12/IL-10 ratio as compared to untreated controls. Both alterations seemed to be induced by interferon-γ (IFN-γ), which is upregulated in T cells and natural killer cells upon ICB. Furthermore, the enhanced IL-12/IL-10 ratio, which favors Th1-prone antitumor T-cell responses, was a consequence of direct interaction of ICB antibodies with DCs. Importantly, the capability of tumor-infiltrating DCs of stimulating peptide-specific or allogeneic T-cell responses in vitro was improved when DCs were derived from ICB-treated mice. The data indicate that ICB therapy is not only effective by directly activating T cells, but also by triggering a complex network, in which DCs play a pivotal role at the interface between innate and adaptive antitumor responses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00262-020-02767-6) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2020-11-03 2021 /pmc/articles/PMC8053142/ /pubmed/33141285 http://dx.doi.org/10.1007/s00262-020-02767-6 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Scheuerpflug, Anne Ahmetlić, Fatima Bauer, Vera Riedel, Tanja Röcken, Martin Mocikat, Ralph The role of dendritic cells for therapy of B-cell lymphoma with immune checkpoint inhibitors |
title | The role of dendritic cells for therapy of B-cell lymphoma with immune checkpoint inhibitors |
title_full | The role of dendritic cells for therapy of B-cell lymphoma with immune checkpoint inhibitors |
title_fullStr | The role of dendritic cells for therapy of B-cell lymphoma with immune checkpoint inhibitors |
title_full_unstemmed | The role of dendritic cells for therapy of B-cell lymphoma with immune checkpoint inhibitors |
title_short | The role of dendritic cells for therapy of B-cell lymphoma with immune checkpoint inhibitors |
title_sort | role of dendritic cells for therapy of b-cell lymphoma with immune checkpoint inhibitors |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053142/ https://www.ncbi.nlm.nih.gov/pubmed/33141285 http://dx.doi.org/10.1007/s00262-020-02767-6 |
work_keys_str_mv | AT scheuerpfluganne theroleofdendriticcellsfortherapyofbcelllymphomawithimmunecheckpointinhibitors AT ahmetlicfatima theroleofdendriticcellsfortherapyofbcelllymphomawithimmunecheckpointinhibitors AT bauervera theroleofdendriticcellsfortherapyofbcelllymphomawithimmunecheckpointinhibitors AT riedeltanja theroleofdendriticcellsfortherapyofbcelllymphomawithimmunecheckpointinhibitors AT rockenmartin theroleofdendriticcellsfortherapyofbcelllymphomawithimmunecheckpointinhibitors AT mocikatralph theroleofdendriticcellsfortherapyofbcelllymphomawithimmunecheckpointinhibitors AT scheuerpfluganne roleofdendriticcellsfortherapyofbcelllymphomawithimmunecheckpointinhibitors AT ahmetlicfatima roleofdendriticcellsfortherapyofbcelllymphomawithimmunecheckpointinhibitors AT bauervera roleofdendriticcellsfortherapyofbcelllymphomawithimmunecheckpointinhibitors AT riedeltanja roleofdendriticcellsfortherapyofbcelllymphomawithimmunecheckpointinhibitors AT rockenmartin roleofdendriticcellsfortherapyofbcelllymphomawithimmunecheckpointinhibitors AT mocikatralph roleofdendriticcellsfortherapyofbcelllymphomawithimmunecheckpointinhibitors |