In contrast to solid tumors, the likely mechanism of action of PD-1 blockade in cHL involves modulation of the tumor microenvironment (TME) with rapid clearance of CD4+ regulatory T cells and PD-L1+ macrophages and withdrawal of pro-survival signals rather than activation of CD8+ cytotoxic T cells [34,35,36]. Here, CD4 is linked to classic Hodgkin lymphoma.