The impact of immune checkpoint inhibitors on the treatment of HL is related to the unique property of HL of being constituted only by a minority of malignant cells (Reed–Stemberg cells) embedded in an abundant microenvironment, whose cells overexpress PD1-PDL1 due to a genetic aberration in the 9p23-24 locus. This evidence concerns the gene CD274 and Hodgkins lymphoma.