Digital spatial profiling of CD4+ T cells in classic Hodgkin lymphoma.

Classic Hodgkin lymphoma (CHL) harbors a small number of Hodgkin-Reed-Sternberg (HRS) cells scattered 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 the tumor microenvironment (TME) of CHL. To elucidate the interaction between HRS cells and CD4+ T cell rosettes, we completed digital spatial profiling to compare the gene expression profiles of CD4+ T cell rosettes and other CD4+ T cells separated from the HRS cells. Immune checkpoint molecules including OX40, programed cell death-1 (PD-1), and cytotoxic T lymphocyte associated protein 4 (CTLA-4) expression was higher in CD4+ T cell rosettes compared to other CD4+ T cells. Immunohistochemistry confirmed variable PD-1, CTLA-4, and OX40 expression in the CD4+ T cell rosettes. This study introduced a new pathological approach to study the CHL TME, and provided deeper insight into CD4+ T cells in CHL.