Overview of cross talk between tumor cells and noncancerous immune cells in the TME of CHL. Interaction between HRS cells and numerous nonmalignant immune cells in the TME are shown according to cell type. These interactions play an important role promoting acquired immune evasion and activation of pathways that support the growth and survival of HRS cells through (1) ligand and receptor interactions, such as PD-1/PD-L1, LAG-3/MHC-II and (2) cytokines and chemokine milieus (eg, CXCL13, TGF-β). Several cross talk mechanisms and related treatment targets are highlighted. CXCL13, chemokine C-X-C motif ligand 13; CXCR5, C-X-C chemokine receptor type 5; IL-3, interleukin 3; TGF- β, transforming growth factor beta.