Mapping the Spatial Dynamics of the CD4+ T Cell Spectrum in Classical Hodgkin Lymphoma

IF 7.1 1区 医学 Q1 PATHOLOGY Modern Pathology Pub Date : 2024-06-25 DOI:10.1016/j.modpat.2024.100551
Victoria Menéndez , José L. Solórzano , Mónica García-Cosío , Laura Cereceda , Eva Díaz , Mónica Estévez , Giovanna Roncador , Zaira Vega , Carlos Montalbán , Arutha Kulasinghe , Juan F. García
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Abstract

As around 25% to 30% of classical Hodgkin lymphoma (cHL) patients with advanced stages do not respond to standard therapies, the tumor microenvironment of cHL is one avenue that may be explored with the aim of improving risk stratification. CD4+ T cells are thought to be one of the main cell types in the tumor microenvironment. However, few immune signatures have been studied, and many of these lack related spatial data. Thus, our aim is to spatially resolve the CD4+ T cell subtypes that influence cHL outcome, depicting new immune signatures or transcriptional patterns that are in crosstalk with the tumor cells. This study was conducted using the NanoString GeoMx digital spatial profiling technology, based on the selection of distinct functional areas of patients’ tissues followed by gene-expression profiling. The goals were to assess the differences in CD4+ T cell populations between tumor-rich and immune-predominant areas defined by different CD30 and PD-L1 expression levels and seek correlations with clinical metadata. Our results depict a complex map of CD4+ T cells with different functions and differentiation states that are enriched at distinct locations, the flux of cytokines and chemokines that could be related to these, and the specific relationships with the clinical outcome.

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绘制典型霍奇金淋巴瘤 CD4+ T 细胞谱的空间动态图。
由于约有25-30%的晚期霍奇金淋巴瘤(cHL)患者对标准疗法无反应,因此可以探索cHL的肿瘤微环境(TME),以改善风险分层。CD4+ T细胞被认为是TME中的主要细胞类型之一。然而,目前对免疫特征的研究还很少,而且其中许多缺乏相关的空间数据。因此,我们的目标是在空间上解析影响 cHL 结果的 CD4+ T 细胞亚型,描绘与肿瘤细胞发生串联的新免疫特征或转录模式。这项研究采用了Nanostring GeoMx DSP技术,首先选择患者组织的不同功能区,然后进行基因表达谱分析。目的是评估由不同 CD30 和 PD-L1 表达水平定义的肿瘤富集区和免疫优势区之间 CD4+ T 细胞群的差异,并寻求与临床元数据的相关性。我们的研究结果描绘了具有不同功能和分化状态的 CD4+ T 细胞在不同位置富集的复杂图谱、可能与之相关的细胞因子和趋化因子通量以及与临床结果的特定关系。
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来源期刊
Modern Pathology
Modern Pathology 医学-病理学
CiteScore
14.30
自引率
2.70%
发文量
174
审稿时长
18 days
期刊介绍: Modern Pathology, an international journal under the ownership of The United States & Canadian Academy of Pathology (USCAP), serves as an authoritative platform for publishing top-tier clinical and translational research studies in pathology. Original manuscripts are the primary focus of Modern Pathology, complemented by impactful editorials, reviews, and practice guidelines covering all facets of precision diagnostics in human pathology. The journal's scope includes advancements in molecular diagnostics and genomic classifications of diseases, breakthroughs in immune-oncology, computational science, applied bioinformatics, and digital pathology.
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