文章：

套细胞淋巴瘤中早期与晚期分化阶段T细胞的定量与谱系分析揭示患者亚群的免疫治疗靶点

Quantification and Profiling of Early and Late Differentiation Stage T Cells in Mantle Cell Lymphoma Reveals Immunotherapeutic Targets in Subsets of Patients

原文发布日期：21 June 2024

DOI: 10.3390/cancers16132289

类型: Article

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英文摘要：

With the aim to advance the understanding of immune regulation in MCL and to identify targetable T-cell subsets, we set out to combine image analysis and spatial omic technology focused on both early and late differentiation stages of T cells. MCL patient tissue (n= 102) was explored using image analysis and GeoMx spatial omics profiling of 69 proteins and 1812 mRNAs. Tumor cells, T helper (TH) cells and cytotoxic (TC) cells of early (CD57−) and late (CD57+) differentiation stage were analyzed. An image analysis workflow was developed based on fine-tuned Cellpose models for cell segmentation and classification. TCand CD57+ subsets of T cells were enriched in tumor-rich compared to tumor-sparse regions. Tumor-sparse regions had a higher expression of several key immune suppressive proteins, tentatively controlling T-cell expansion in regions close to the tumor. We revealed that T cells in late differentiation stages (CD57+) are enriched among MCL infiltrating T cells and are predictive of an increased expression of immune suppressive markers. CD47, IDO1 and CTLA-4 were identified as potential targets for patients with T-cell-rich MCL TIME, while GITR might be a feasible target for MCL patients with sparse T-cell infiltration. In subgroups of patients with a high degree of CD57+ TC-cell infiltration, several immune checkpoint inhibitors, including TIGIT, PD-L1 and LAG3 were increased, emphasizing the immune-suppressive features of this highly differentiated T-cell subset not previously described in MCL.

摘要翻译： 

为深化对套细胞淋巴瘤（MCL）免疫调控机制的理解并识别可靶向的T细胞亚群，本研究结合图像分析与空间组学技术，聚焦于T细胞早期及晚期分化阶段。通过对102例MCL患者组织样本进行图像分析及GeoMx空间组学检测（涵盖69种蛋白质及1812个mRNA），我们分析了肿瘤细胞、辅助性T细胞（TH）以及处于早期分化（CD57−）与晚期分化（CD57+）阶段的细胞毒性T细胞（TC）。研究建立了基于精细化Cellpose模型的图像分析流程，用于细胞分割与分类。结果显示，与肿瘤稀疏区域相比，肿瘤富集区域中TC细胞及CD57+ T细胞亚群显著增多。肿瘤稀疏区域则高表达多种关键免疫抑制蛋白，可能调控邻近肿瘤区域的T细胞扩增。研究发现，处于晚期分化阶段（CD57+）的T细胞在MCL浸润T细胞中富集，且可预测免疫抑制标志物表达升高。CD47、IDO1和CTLA-4被确定为T细胞富集型MCL肿瘤免疫微环境（TIME）的潜在治疗靶点，而GITR可能适用于T细胞稀疏型MCL患者。在CD57+ TC细胞高度浸润的患者亚组中，包括TIGIT、PD-L1和LAG3在内的多种免疫检查点抑制剂表达上调，凸显了这一高分化T细胞亚群在MCL中未被充分认识的免疫抑制特征。

原文链接：

Quantification and Profiling of Early and Late Differentiation Stage T Cells in Mantle Cell Lymphoma Reveals Immunotherapeutic Targets in Subsets of Patients