Model of PD-1:PD-L1 and CTLA-4:CD86 interactions in cHL. HRS cells (purple) express PD-L1 (and PD-L2) and CD86. TAMs (blue) that are in proximity to HRS cells frequently coexpress both PD-L1 and CD86, likely in response to local cytokine production, and thereby significantly increase the total amount of these ligands in proximity to the malignant cells. PD-L1 and CD86 on TAMs and HRS cells are available to bind PD-1–positive/CD4-positive T cells (green) and CTLA-4–positive/CD4-positive T cells (yellow). PD-1–positive T cells (previously shown)⁶  and CTLA-4–positive T cells are specifically enriched in the vicinity of PD-L1–positive/CD86-positive HRS cells.