Digital Spatial Profiling reveals tumor microenvironment of Hodgkin-like adult T-cell leukemia/lymphoma.

Hodgkin-like adult T-cell leukemia/lymphoma (ATLL) is a rare subtype of ATLL harboring human T cell lymphotropic virus type-1-infected Hodgkin-Reed-Sternberg (HRS)-like cells and small to medium CD4+ T cells, which histologically mimics classic Hodgkin lymphoma (CHL). CD30+ tumor cells or HRS cells are surrounded by CD4+ non-neoplastic T cells in a rosette-like manner in CHL. Interaction between HRS cells and surrounding CD4+ T cells is important for tumor microenvironment (TME) in CHL. Tumor microenvironment of Hodgkin-like ATLL remains unclear. Here, Digital Spatial Profiling was performed on Hodgkin-like ATLL to elucidate the interaction between HRS-like cells and CD4+ T cells in Hodgkin-like ATLL. We identified CD4+ T cells expressing co-stimulatory molecules, CD28 and inducible T cell co-stimulator (ICOS), in CD4+ T cells surrounding the HRS-like cells than in those apart from HRS-like cells. Immunohistochemistry was performed in 11 cases of Hodgkin-like ATLL, which detected distinct CD4+ T cells expressing CD28 in a rosette-like manner around HRS-like cells. HRS-like cells widely expressed CD80 and CD86, which suggested CD28-CD80/CD86 interaction was important in pathogenesis of Hodgkin-like ATLL. ICOS and immune checkpoint molecules, including T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) and programmed death-1 (PD-1) were also variably expressed in CD4+ T cells surrounding HRS-like cells. Our findings provide new insights into the tumor microenvironment of Hodgkin-like ATLL and implicate a new therapeutic strategy targeting these molecules. Total 12 areas of interest from 4 Hodgkin-like ATLL were sequenced using GeoMx Digital Spatial Profiler (Nanostring Technologies), with the Human Whole Transcriptome Altas (18,000+ genes)