Digital Spatial Profiling of tumor microenvironment of classic Hodgkin lymphoma.

Classic Hodgkin lymphoma (CHL) harbors a small number of Hodgkin-Reed-Sternberg (HRS) cells scattering among numerous lymphocytes. HRS cells are surrounded by distinct CD4+ T cells in a rosette-like manner. These CD4+ T cell rosettes play an important role in tumor microenvironment (TME) of CHL. To elucidate the interaction between HRS cells and CD4+ T cell rosettes, we performed digital spatial profiling (DSP) and compared gene expression profile between CD4+ T cell rosettes and other CD4+ cells separated from HRS cells. programed cell death-1 (PD-1) and tumor necrosis factor receptor superfamily member (TNFRSF) 4 were significantly highly expressed in CD4+ T cell rosettes than others. Immunohistochemistry confirmed PD-1 and TNFRSF4-expressing CD4+ T cell rosettes. This study introduced the new pathological approach to TME and provided deeper insight to CD4+ T cells in CHL. Total 12 areas of interest from a case of CHL were sequenced using GeoMx Digital Spatial Profiler (Nanostring Technologies), with the Human Whole Transcriptome Altas (18,000+ genes)