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.
结节性淋巴细胞为主型霍奇金淋巴瘤（NLPHL）是一种罕见的淋巴瘤，其肿瘤B细胞稀疏且预后良好。然而，NLPHL的变异生长模式常表现为晚期疾病、可进展为T细胞/组织细胞丰富的大B细胞淋巴瘤（THRLBCL），且预后较差。我们采用高通量多重成像及单细胞空间图谱分析技术，研究了NLPHL与THRLBCL的肿瘤微环境（TME）。研究结果显示，典型NLPHL、变异型NLPHL与THRLBCL在TME组成及空间构型上存在显著差异：典型NLPHL富含辅助性T细胞亚群，而THRLBCL则富含细胞毒性T细胞和巨噬细胞。肿瘤B细胞的大小和数量在典型NLPHL中最低，变异型NLPHL次之，THRLBCL中最高；而TME中B细胞的数量变化趋势则相反。所有NLPHL病例中均可见CD4/CD8双阳性T细胞，但大多数THRLBCL中不存在，且这类细胞在空间分布上与LP细胞及TFH玫瑰花结保持距离。通过独立病例队列进一步证实，巨噬细胞/单核细胞含量的差异有助于区分NLPHL的E型模式与THRLBCL。我们的研究结果验证了当前分类方法的科学性，并为优化此类淋巴瘤患者的临床管理提供了新的见解。
肿瘤(癌症)患者之家