Clinical & translational immunology · 2025
High-dimensional spectral cytometry identifies follicular regulatory CD8+ T cells in diffuse large B-cell lymphoma.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Díaz Herrero Alba, Le Phuong-Ha, Renaud Loic, Meignin Véronique, Thieblemont Catherine, Blanc Véronique, Soumelis Vassili, Tonnerre Pierre
Аннотация
OBJECTIVES: Diffuse large B-cell lymphoma (DLBCL) constitutes 30-40% of non-Hodgkin lymphoma cases. Despite therapeutic advances, persistence of relapsed cases has been linked to the complex tumor microenvironment (TME) and its interactions with lymphoma cells. In particular, characterising T-cell subsets, including rare cell types, and their interplay with the remaining TME is crucial for unravelling DLBCL pathogenesis and refining therapeutic strategies.
METHODS: Using flow and spectral cytometry with unsupervised analysis, we investigated T-cell subpopulations across DLBCL biopsies and control lymph nodes (LN). We also inferred communication pathways between T cells and other immune cells in the TME based on the correlation of ligand-receptor expression.
RESULTS: Our analysis revealed a higher frequency of CD8+ follicular regulatory T (Tfr) cells in DLBCL biopsies compared to control LN. These cells exhibited an effector-memory phenotype (CD45RA- CCR7-), expressed follicular markers (PD-1+ CXCR5+) and had a regulatory profile (CD127- CD25+) along with an activation/co-stimulatory signature (HLA-DR+, ICOS+, CD95+). Correlation analysis highlighted a co-stimulatory interaction between lymphoma B cells and CD8+ Tfr cells through the ICOS/ICOSL pathway, which may contribute to a protumor effect. Validation in independent scRNAseq and flow cytometry datasets confirmed the notable prevalence of CD8+ Tfr cells in DLBCL biopsies.
CONCLUSIONS: Our study highlights the utility of high-dimensional computational cytometry in elucidating T-cell subpopulations, including an increased frequency of CD8+ follicular regulatory T cells and their communication patterns within the DLBCL TME. This unbiased approach sheds light on novel cellular mechanisms in DLBCL, uncovering potential targets and biomarkers for immunotherapy.
METHODS: Using flow and spectral cytometry with unsupervised analysis, we investigated T-cell subpopulations across DLBCL biopsies and control lymph nodes (LN). We also inferred communication pathways between T cells and other immune cells in the TME based on the correlation of ligand-receptor expression.
RESULTS: Our analysis revealed a higher frequency of CD8+ follicular regulatory T (Tfr) cells in DLBCL biopsies compared to control LN. These cells exhibited an effector-memory phenotype (CD45RA- CCR7-), expressed follicular markers (PD-1+ CXCR5+) and had a regulatory profile (CD127- CD25+) along with an activation/co-stimulatory signature (HLA-DR+, ICOS+, CD95+). Correlation analysis highlighted a co-stimulatory interaction between lymphoma B cells and CD8+ Tfr cells through the ICOS/ICOSL pathway, which may contribute to a protumor effect. Validation in independent scRNAseq and flow cytometry datasets confirmed the notable prevalence of CD8+ Tfr cells in DLBCL biopsies.
CONCLUSIONS: Our study highlights the utility of high-dimensional computational cytometry in elucidating T-cell subpopulations, including an increased frequency of CD8+ follicular regulatory T cells and their communication patterns within the DLBCL TME. This unbiased approach sheds light on novel cellular mechanisms in DLBCL, uncovering potential targets and biomarkers for immunotherapy.