| Autor: |
Dannis G. van Vuurden, Lennart Kester, Cristian Ruiz-Moreno, Peter Brazda, Mariette E.G. Kranendonk, Wout Megchelenbrink, Brigit te Pas, Hendrik G. Stunnenberg, Kim Boshuisen, Jasper Van der Lugt, Farid Keramati, Helena C. Besse |
| Rok vydání: |
2021 |
| Předmět: |
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| Popis: |
Macrophage (Mϕ) repolarization from a pro-tumor, immunosuppressive phenotype towards an anti-tumor, pro-inflammatory state represents a promising therapeutic strategy in patients with cancer1. Successful reprogramming of Mϕ in a clinical setting has not been documented. Here, we traced the evolution at single-cell resolution of a diffuse midline glioma (DMG) with H3K27M mutation which metastasized in the abdomen after placing a ventriculoperitoneal (VP) shunt and exploited this information for therapeutic decision-making. The primary tumor showed a complex cellular and genomic landscape characterized by heterogeneous cancer cells and a tumor-supportive immune microenvironment. Upon metastasis, malignant cells populated the peritoneum and triggered a massive anti-inflammatory immune cell infiltration and expansion of myeloid-derived suppressor cells (MDSCs) in peripheral blood. Hydroxychloroquine adjuvant treatment started to overcome the immunosuppressive milieu, which resulted in a decrease in peritoneal cancer cells and pro-tumor innate immune cells. Importantly, an emergence of anti-tumor, pro-inflammatory macrophages and cytotoxic T-cells was observed, accompanied by the activation of monocytes in the blood. Our study advocates the employment of single-cell technologies to better understand and inspire therapeutic regimens in patients with cancer. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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