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| 001 | 153759 | ||
| 005 | 20251118111342.0 | ||
| 024 | 7 | _ | |a 10.1038/s41467-020-14642-0 |2 doi |
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| 037 | _ | _ | |a DKFZ-2020-00444 |
| 041 | _ | _ | |a eng |
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| 100 | 1 | _ | |a Aslan, Katrin |0 P:(DE-HGF)0 |b 0 |e First author |
| 245 | _ | _ | |a Heterogeneity of response to immune checkpoint blockade in hypermutated experimental gliomas. |
| 260 | _ | _ | |a [London] |c 2020 |b Nature Publishing Group UK |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
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| 500 | _ | _ | |a #EA:D170#LA:D170# / HI-TRON / #DKFZ-MOST-Ca188# |
| 520 | _ | _ | |a Intrinsic malignant brain tumors, such as glioblastomas are frequently resistant to immune checkpoint blockade (ICB) with few hypermutated glioblastomas showing response. Modeling patient-individual resistance is challenging due to the lack of predictive biomarkers and limited accessibility of tissue for serial biopsies. Here, we investigate resistance mechanisms to anti-PD-1 and anti-CTLA-4 therapy in syngeneic hypermutated experimental gliomas and show a clear dichotomy and acquired immune heterogeneity in ICB-responder and non-responder tumors. We made use of this dichotomy to establish a radiomic signature predicting tumor regression after pseudoprogression induced by ICB therapy based on serial magnetic resonance imaging. We provide evidence that macrophage-driven ICB resistance is established by CD4 T cell suppression and Treg expansion in the tumor microenvironment via the PD-L1/PD-1/CD80 axis. These findings uncover an unexpected heterogeneity of response to ICB in strictly syngeneic tumors and provide a rationale for targeting PD-L1-expressing tumor-associated macrophages to overcome resistance to ICB. |
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| 700 | 1 | _ | |a Liuzzi, Anna Rita |b 4 |
| 700 | 1 | _ | |a Núñez, Nicolás Gonzalo |0 0000-0003-3837-270X |b 5 |
| 700 | 1 | _ | |a De Feo, Donatella |b 6 |
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| 773 | _ | _ | |a 10.1038/s41467-020-14642-0 |g Vol. 11, no. 1, p. 931 |0 PERI:(DE-600)2553671-0 |n 1 |p 931 |t Nature Communications |v 11 |y 2020 |x 2041-1723 |
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