HPV阳性口咽癌中与淋巴结状态相关的空间免疫程序在淋巴滤泡区域和瘤周扁桃体组织之间存在差异
Spatial immune programs associated with nodal status differ between lymphoid follicular regions and peritumoral tonsillar tissue in HPV-positive oropharyngeal cancer.
摘要(中文译文)
在人乳头状瘤病毒（HPV）阳性口咽癌（OPC）中，淋巴结转移较为常见，但其生物学及预后意义尚未被完全阐明。对于肿瘤相关次级淋巴结构内免疫程序的空间组织方式，目前所知更少。本研究通过空间区分淋巴滤泡区域（LFRs）与无肿瘤的瘤周扁桃体组织（PTTs），对扁桃体来源的HPV阳性OPC中的免疫程序进行了分析。LFRs采用空间转录组学分析，PTTs采用批量转录组学分析。对既往生成的GeoMx数字空间分析仪及批量微阵列数据集进行再分析，以探究区室特异性免疫程序。根据淋巴结状态，采用单样本基因集富集分析评估免疫通路活性。在LFRs和PTTs中均识别出与淋巴结状态相关的区室特异性免疫程序。在LFRs中，淋巴结阳性病例显示干样、前耗竭及T细胞活性程序的富集，并伴有炎症及干扰素相关信号。相比之下，淋巴结阴性的PTTs则显示干样、前耗竭及T细胞活性程序的富集，同时伴有IL2-STAT5及TGF-β信号，而无明显的炎症激活。这些发现表明，相同的免疫通路因其空间定位不同而表现出不同的生物学关联。在HPV阳性OPC中，与淋巴结转移相关的免疫程序因空间免疫背景而异。区分LFRs与无肿瘤的PTTs，为超越批量组织分析解读免疫程序提供了框架，并凸显了空间免疫组织在塑造生物学解读中的重要性。由于空间转录组学分析仅在有限数量的患者中进行，这些发现应被视为探索性结果，并需在更大规模的独立队列中加以验证。
Abstract
In human papillomavirus (HPV)-positive oropharyngeal cancer (OPC), lymph node metastasis is common, yet its biological and prognostic implications remain incompletely understood. Less is known about the spatial organization of immune programs within tumor-associated secondary lymphoid structures. Immune programs were analyzed by spatially distinguishing lymphoid follicular regions (LFRs) from tumor-free peritumoral tonsillar tissues (PTTs) in palatine tonsil-derived HPV-positive OPC. LFRs were analyzed using spatial transcriptomics and PTTs using bulk transcriptomics. Previously generated GeoMx Digital Spatial Profiler and bulk microarray datasets were reanalyzed to investigate compartment-specific immune programs. Immune pathway activity was assessed using single-sample gene set enrichment analysis according to nodal status. Compartment-specific immune programs associated with nodal status were identified in both LFRs and PTTs. In LFRs, nodal-positive cases showed enrichment of stem-like, pre-exhausted, and T-cell activity programs accompanied by inflammatory and interferon-associated signaling. In contrast, nodal-negative PTTs exhibited enrichment of stem-like, pre-exhausted, and T-cell activity programs together with IL2-STAT5 and TGF-β signaling, without overt inflammatory activation. These findings indicate that identical immune pathways exhibit distinct biological associations depending on their spatial localization. Immune programs associated with nodal metastasis in HPV-positive OPC vary according to spatial immune context. Distinguishing LFRs from tumor-free PTTs provides a framework for interpreting immune programs beyond bulk tissue analysis and highlights the importance of spatial immune organization in shaping biological interpretation. Because the spatial transcriptomic analyses were performed in a limited number of patients, these findings should be considered exploratory and require validation in larger independent cohorts.
如何引用
AMA
Naohiro Wakisaka, Makiko Moriyama-Kita, Satoru Kondo, Eiji Kobayashi, Takayoshi Ueno, Yosuke Nakanishi, et al. Spatial immune programs associated with nodal status differ between lymphoid follicular regions and peritumoral tonsillar tissue in HPV-positive oropharyngeal cancer.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1905992.
APA
Naohiro Wakisaka, Makiko Moriyama-Kita, Satoru Kondo, Eiji Kobayashi, Takayoshi Ueno, Yosuke Nakanishi, et al (2026). Spatial immune programs associated with nodal status differ between lymphoid follicular regions and peritumoral tonsillar tissue in HPV-positive oropharyngeal cancer.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1905992
GB/T 7714
Naohiro Wakisaka, Makiko Moriyama-Kita, Satoru Kondo, Eiji Kobayashi, Takayoshi Ueno, Yosuke Nakanishi, et al. Spatial immune programs associated with nodal status differ between lymphoid follicular regions and peritumoral tonsillar tissue in HPV-positive oropharyngeal cancer.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1905992.
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