Spatial analysis identifies DC niches as predictors of pembrolizumab therapy in head and neck squamous cell cancer.

IF 11.7 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2025-05-20 Epub Date: 2025-04-30 DOI:10.1016/j.xcrm.2025.102100

Juhyun Oh, Jan Hoelzl, Jonathan C T Carlson, Ruben Bill, Hannah M Peterson, William C Faquin, Mikael J Pittet, Sara I Pai, Ralph Weissleder

{"title":"Spatial analysis identifies DC niches as predictors of pembrolizumab therapy in head and neck squamous cell cancer.","authors":"Juhyun Oh, Jan Hoelzl, Jonathan C T Carlson, Ruben Bill, Hannah M Peterson, William C Faquin, Mikael J Pittet, Sara I Pai, Ralph Weissleder","doi":"10.1016/j.xcrm.2025.102100","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102100"},"PeriodicalIF":11.7000,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147904/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Reports Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.xcrm.2025.102100","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/30 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

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.

查看原文本刊更多论文

空间分析确定DC利基作为头颈部鳞状细胞癌派姆单抗治疗的预测因子。

头颈部鳞状细胞癌（HNSCC）对抗程序性细胞死亡蛋白1 （PD-1）治疗表现出不同的反应，这可以部分解释为肿瘤的联合阳性评分（CPS）和局部肿瘤微环境（TME）中程序性死亡配体1 （PD-L1）的免疫细胞表达。为了更好地定义与治疗效果相关的TME免疫决定因素，我们在派姆单抗治疗前对n = 48例HNSCC肿瘤患者进行了研究。我们的研究结合了快速生物正交多重染色方法和全片成像的计算分析，以捕捉TME的单细胞空间异质性和复杂性。通过分析6316个视场（fov），我们在整个组织切片上提供全面的PD-L1表型和细胞接近性分析。虽然没有PD-L1指标能充分预测反应，但我们发现CCR7+树突状细胞（dc）在壁龛中的空间组织比单独使用CPS更好地预测患者的总体生存。这项研究强调了理解免疫网络空间背景对免疫治疗的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.