CD4 and classic Hodgkin lymphoma: While only 1% of tumor tissue is composed of malignant Reed–Sternberg (RS) cells, the remaining 99% of cHL tissue comprises the TME and includes numerous inflammatory cells including B-cells, T-cells [CD4+ T-helper cells, regulatory T-cells (Tregs), and cytotoxic CD8+ T-cells], macrophages, eosinophils, neutrophils, plasma cells, dendritic cells, and fibroblasts, all meticulously orchestrated by the dysregulated secretion of chemokines and cytokines from both TME and RS cells (11).