PDF(Pubmed)
Abstract：
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma with sparse tumor B-cells and a favorable prognosis. Variant growth patterns of NLPHL, however, often show advanced stage, progression to T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) and a worse prognosis. We studied the tumor microenvironment (TME) of NLPHL and THRLBCL using highplex imaging and spatial profiling at the single cell level. Our findings show distinct differences in TME composition and spatial configuration that differ among typical and variant NLPHL and THRLBCL. Typical NLPHL show abundant helper T-cell subsets, while THRLBCL show abundant cytotoxic T-cells and macrophages. Tumor B-cell size and content is lowest in typical NLPHL, followed by variant NLPHL, and highest in THRLBCL, whereas an opposite trend characterized TME B-cells. CD4/CD8 double-positive T-cells are seen in all NLPHL but not in the majority of THRLBCL and are spatially distant from LP-cells and TFH-rosettes. The differences in macrophage/monocyte content in distinguishing NLPHL pattern E from THRLBCL is further corroborated in independent cohorts of cases. Our results validate the current approach to classification and in addition provide novel insights that could be leveraged to refine clinical management for patients with this spectrum of lymphomas.
摘要：
结节性淋巴细胞为主的霍奇金淋巴瘤（NLPHL）是一种罕见的淋巴瘤，肿瘤B细胞稀疏，预后良好。NLPHL的变异生长模式，然而,经常表现出先进的舞台，进展为富含T细胞/组织细胞的大B细胞淋巴瘤（THRLBCL）和较差的预后。我们研究了NLPHL和THRLBCL的肿瘤微环境（TME），使用了单细胞水平的高速成像和空间分析。我们的发现显示TME组成和空间构型的明显差异，在典型和变体NLPHL和THRLBCL之间存在差异。典型的NLPHL显示丰富的辅助性T细胞亚群，而THRLBCL显示丰富的细胞毒性T细胞和巨噬细胞。肿瘤B细胞的大小和含量在典型的NLPHL中是最低的,其次是变异NLPHL，在THRLBCL中最高，而相反的趋势表征TMEB细胞。CD4/CD8双阳性T细胞见于所有NLPHL，但未见于大多数THRLBCL，并且在空间上远离LP细胞和TFH玫瑰花环。巨噬细胞/单核细胞含量在区分NLPHL模式E与THRLBCL中的差异在独立病例组中得到进一步证实。我们的结果验证了目前的分类方法，此外还提供了新的见解，可以利用这些见解来完善患有这种淋巴瘤的患者的临床管理。
