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The immune suppressive microenvironment affects efficacy of radio‐immunotherapy in brain metastasis
The tumor microenvironment in brain metastases is characterized by high myeloid cell content associated with immune suppressive and cancer‐permissive functions. Moreover, brain metastases induce the recruitment of lymphocytes. Despite their presence, T‐cell‐directed therapies fail to elicit effectiv...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103101/ https://www.ncbi.nlm.nih.gov/pubmed/33755340 http://dx.doi.org/10.15252/emmm.202013412 |
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author | Niesel, Katja Schulz, Michael Anthes, Julian Alekseeva, Tijna Macas, Jadranka Salamero‐Boix, Anna Möckl, Aylin Oberwahrenbrock, Timm Lolies, Marco Stein, Stefan Plate, Karl H Reiss, Yvonne Rödel, Franz Sevenich, Lisa |
author_facet | Niesel, Katja Schulz, Michael Anthes, Julian Alekseeva, Tijna Macas, Jadranka Salamero‐Boix, Anna Möckl, Aylin Oberwahrenbrock, Timm Lolies, Marco Stein, Stefan Plate, Karl H Reiss, Yvonne Rödel, Franz Sevenich, Lisa |
author_sort | Niesel, Katja |
collection | PubMed |
description | The tumor microenvironment in brain metastases is characterized by high myeloid cell content associated with immune suppressive and cancer‐permissive functions. Moreover, brain metastases induce the recruitment of lymphocytes. Despite their presence, T‐cell‐directed therapies fail to elicit effective anti‐tumor immune responses. Here, we seek to evaluate the applicability of radio‐immunotherapy to modulate tumor immunity and overcome inhibitory effects that diminish anti‐cancer activity. Radiotherapy‐induced immune modulation resulted in an increase in cytotoxic T‐cell numbers and prevented the induction of lymphocyte‐mediated immune suppression. Radio‐immunotherapy led to significantly improved tumor control with prolonged median survival in experimental breast‐to‐brain metastasis. However, long‐term efficacy was not observed. Recurrent brain metastases showed accumulation of blood‐borne PD‐L1(+) myeloid cells after radio‐immunotherapy indicating the establishment of an immune suppressive environment to counteract re‐activated T‐cell responses. This finding was further supported by transcriptional analyses indicating a crucial role for monocyte‐derived macrophages in mediating immune suppression and regulating T‐cell function. Therefore, selective targeting of immune suppressive functions of myeloid cells is expected to be critical for improved therapeutic efficacy of radio‐immunotherapy in brain metastases. |
format | Online Article Text |
id | pubmed-8103101 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81031012021-05-10 The immune suppressive microenvironment affects efficacy of radio‐immunotherapy in brain metastasis Niesel, Katja Schulz, Michael Anthes, Julian Alekseeva, Tijna Macas, Jadranka Salamero‐Boix, Anna Möckl, Aylin Oberwahrenbrock, Timm Lolies, Marco Stein, Stefan Plate, Karl H Reiss, Yvonne Rödel, Franz Sevenich, Lisa EMBO Mol Med Articles The tumor microenvironment in brain metastases is characterized by high myeloid cell content associated with immune suppressive and cancer‐permissive functions. Moreover, brain metastases induce the recruitment of lymphocytes. Despite their presence, T‐cell‐directed therapies fail to elicit effective anti‐tumor immune responses. Here, we seek to evaluate the applicability of radio‐immunotherapy to modulate tumor immunity and overcome inhibitory effects that diminish anti‐cancer activity. Radiotherapy‐induced immune modulation resulted in an increase in cytotoxic T‐cell numbers and prevented the induction of lymphocyte‐mediated immune suppression. Radio‐immunotherapy led to significantly improved tumor control with prolonged median survival in experimental breast‐to‐brain metastasis. However, long‐term efficacy was not observed. Recurrent brain metastases showed accumulation of blood‐borne PD‐L1(+) myeloid cells after radio‐immunotherapy indicating the establishment of an immune suppressive environment to counteract re‐activated T‐cell responses. This finding was further supported by transcriptional analyses indicating a crucial role for monocyte‐derived macrophages in mediating immune suppression and regulating T‐cell function. Therefore, selective targeting of immune suppressive functions of myeloid cells is expected to be critical for improved therapeutic efficacy of radio‐immunotherapy in brain metastases. John Wiley and Sons Inc. 2021-03-23 2021-05-07 /pmc/articles/PMC8103101/ /pubmed/33755340 http://dx.doi.org/10.15252/emmm.202013412 Text en © 2021 The Authors. Published under the terms of the CC BY 4.0 license https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Niesel, Katja Schulz, Michael Anthes, Julian Alekseeva, Tijna Macas, Jadranka Salamero‐Boix, Anna Möckl, Aylin Oberwahrenbrock, Timm Lolies, Marco Stein, Stefan Plate, Karl H Reiss, Yvonne Rödel, Franz Sevenich, Lisa The immune suppressive microenvironment affects efficacy of radio‐immunotherapy in brain metastasis |
title | The immune suppressive microenvironment affects efficacy of radio‐immunotherapy in brain metastasis |
title_full | The immune suppressive microenvironment affects efficacy of radio‐immunotherapy in brain metastasis |
title_fullStr | The immune suppressive microenvironment affects efficacy of radio‐immunotherapy in brain metastasis |
title_full_unstemmed | The immune suppressive microenvironment affects efficacy of radio‐immunotherapy in brain metastasis |
title_short | The immune suppressive microenvironment affects efficacy of radio‐immunotherapy in brain metastasis |
title_sort | immune suppressive microenvironment affects efficacy of radio‐immunotherapy in brain metastasis |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103101/ https://www.ncbi.nlm.nih.gov/pubmed/33755340 http://dx.doi.org/10.15252/emmm.202013412 |
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