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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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Main Authors: Oh, Juhyun (Author) , Hölzl, Jan (Author) , Carlson, Jonathan C. T. (Author) , Bill, Ruben (Author) , Peterson, Hannah M. (Author) , Faquin, William C. (Author) , Pittet, Mikael J. (Author) , Pai, Sara I. (Author) , Weissleder, Ralph (Author)
Format: Article (Journal)
Language:English
Published: 20 May 2025
In: Cell reports. Medicine
Year: 2025, Volume: 6, Issue: 5, Pages: 1-22
ISSN:2666-3791
DOI:10.1016/j.xcrm.2025.102100
Online Access: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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Author Notes: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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Summary: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.
Item Description:Gesehen am 12.01.2026
Physical Description:Online Resource
ISSN:2666-3791
DOI:10.1016/j.xcrm.2025.102100

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