Spatial Phenotyping of Nodular Lymphocyte Predominant Hodgkin Lymphoma and T-cell/Histiocyte-Rich Large B-cell Lymphoma

Abstract

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, show advanced stage, progression to T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) and a worse prognosis. We studied the spatial configuration of the tumor microenvironment (TME) of NLPHL and THRLBCL using highplex imaging to capture single-cell parameters including spatial localization in 20 patient samples of NLPHL and THRLBCL. Our findings show distinct spatial configurations and TME composition that differ among typical and variant NLPHL, and THRLBCL. Tumor B-cell size and content was lowest in typical NLPHL, followed by variant NLPHL, and highest in THRLBCL, whereas an opposite trend characterized TME B-cells. Typical NLPHL showed abundant helper T-cell subsets, while THRLBCL showed abundant cytotoxic T-cells and monocytes. Spatial analysis further revealed specific interactions typical of NLPHL patterns and THRLBCL. CD4/CD8 double-positive T-cells were detected in all NLPHL but not in the majority of THRLBCL, and were found to be spatially distant from tumor B-cells and TFH-rosettes. We conclude that our results provide valuable insights into immunoarchitectural configurations that inform differences in biologic behavior and could aid in the development of future therapeutics for patients affected by this spectrum of lymphomas.