Katja Niesel, Michael Schulz, Julian Anthes, Tijna Alekseeva, Jadranka Macas, Anna Salamero-Boix, Aylin Möckl, Timm Oberwahrenbrock, Marco Lolies, Stefan Stein, Karl Plate, Yvonne Reiss, Franz Rödel, Lisa Sevenich
- 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 experi- mental breast-to-brain metastasis. However, long-term efficacy was not observed. Recurrent brain metastases showed accumula- tion of blood-borne PD-L1+ myeloid cells after radio-immunother- apy indicating the establishment of an immune suppressive environment to counteract re-activated T-cell responses. This finding was further supported by transcriptional analyses indicat- ing 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.
MetadatenAuthor: | Katja Niesel, Michael Schulz, Julian Anthes, Tijna Alekseeva, Jadranka Macas, Anna Salamero-Boix, Aylin Möckl, Timm Oberwahrenbrock, Marco Lolies, Stefan Stein, Karl Plate, Yvonne Reiss, Franz RödelORCiDGND, Lisa Sevenich |
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URN: | urn:nbn:de:hebis:30:3-615482 |
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DOI: | https://doi.org/10.15252/emmm.202013412 |
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ISSN: | 1757-4684 |
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Parent Title (English): | EMBO molecular medicine |
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Publisher: | Wiley-VCH |
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Place of publication: | Weinheim |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2021/03/23 |
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Date of first Publication: | 2021/03/23 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2021/07/21 |
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Tag: | brain cancer; checkpoint inhibitors; microglia; tumor microenvironment; tumor-associated macrophages |
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Volume: | 13 |
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Issue: | 5, art. e13412 |
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Page Number: | 19 |
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First Page: | 1 |
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Last Page: | 19 |
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HeBIS-PPN: | 484657763 |
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Institutes: | Biowissenschaften |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung 4.0 |
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