Spatial analysis identifies DC niches as predictors of pembrolizumab therapy in head and neck squamous cell cancer
Head and neck squamous cell carcinoma (HNSCC) shows variable response to anti-programmed cell death protein 1 (PD-1) therapy, which can be partially explained by a combined positive score (CPS) of tumor and immune cell expression of programmed death-ligand 1 (PD-L1) within the local tumor microenvir...
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| Hauptverfasser: | , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
20 May 2025
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| In: |
Cell reports. Medicine
Year: 2025, Jahrgang: 6, Heft: 5, Pages: 1-22 |
| ISSN: | 2666-3791 |
| DOI: | 10.1016/j.xcrm.2025.102100 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.xcrm.2025.102100 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S2666379125001739 
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| Verfasserangaben: | Juhyun Oh, Jan Hoelzl, Jonathan C.T. Carlson, Ruben Bill, Hannah M. Peterson, William C. Faquin, Mikael J. Pittet, Sara I. Pai, and Ralph Weissleder |
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| 245 | 1 | 0 | |a Spatial analysis identifies DC niches as predictors of pembrolizumab therapy in head and neck squamous cell cancer |c Juhyun Oh, Jan Hoelzl, Jonathan C.T. Carlson, Ruben Bill, Hannah M. Peterson, William C. Faquin, Mikael J. Pittet, Sara I. Pai, and Ralph Weissleder |
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| 520 | |a Head and neck squamous cell carcinoma (HNSCC) shows variable response to anti-programmed cell death protein 1 (PD-1) therapy, which can be partially explained by a combined positive score (CPS) of tumor and immune cell expression of programmed death-ligand 1 (PD-L1) within the local tumor microenvironment (TME). To better define TME immune determinants associated with treatment efficacy, we conduct a study of n = 48 HNSCC tumors from patients prior to pembrolizumab therapy. Our investigation combines a rapid bioorthogonal multiplex staining method with computational analysis of whole-slide imaging to capture the single-cell spatial heterogeneity and complexity of the TME. Analyzing 6,316 fields of view (FOVs), we provide comprehensive PD-L1 phenotyping and cell proximity assays across the entirety of tissue sections. While none of the PD-L1 metrics adequately predict response, we find that the spatial organization of CCR7+ dendritic cells (DCs) in niches better predicts overall patient survival than CPS alone. This study highlights the importance of understanding the spatial context of immune networks for immunotherapy. | ||
| 650 | 4 | |a biomarkers | |
| 650 | 4 | |a head and neck cancer | |
| 650 | 4 | |a immunotherapy | |
| 650 | 4 | |a microscopy | |
| 650 | 4 | |a spatial biology | |
| 700 | 1 | |a Hölzl, Jan |e VerfasserIn |0 (DE-588)1386470058 |0 (DE-627)1948490838 |4 aut | |
| 700 | 1 | |a Carlson, Jonathan C. T. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bill, Ruben |e VerfasserIn |4 aut | |
| 700 | 1 | |a Peterson, Hannah M. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Faquin, William C. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Pittet, Mikael J. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Pai, Sara I. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Weissleder, Ralph |e VerfasserIn |4 aut | |
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