| Autor: |
Niesel, Katja, Schulz, Michael, Anthes, Julian, Alekseeva, Tijna, Macas, Jadranka, Salamero-Boix, Anna, Möckl, Aylin, Oberwahrenbrock, Timm, Lolies, Marco, Stein, Stefan, Plate, Karl, Reiss, Yvonne, Rödel, Franz, Sevenich, Lisa |
| Přispěvatelé: |
Publica |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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