Checkpoint blockade therapy resistance in Hodgkin's lymphoma Antonino Carbone, Annunziata Gloghini  The Lancet  Volume 392, Issue 10154, Pages 1194-1196 (October 2018) DOI: 10.1016/S0140-6736(18)31867-1 Copyright © 2018 Elsevier Ltd Terms and Conditions

Figure Interactions between PD-1 and its ligands PD-L1 and PD-L2 in the classical Hodgkin's lymphoma microenvironment (A) An antigen-presenting cell (here, a dendritic cell is shown), after activation in a lymph node, expresses PD-L1 on its surface. PD-L1 binds PD-1 on T cells and regulates their activity. (B) In classical Hodgkin's lymphoma, PD-L1 is also expressed by Hodgkin and Reed-Sternberg (HRS) cells. Here, PD-L1 binds PD-1 on CD4+ and CD8+ T cells, suppressing T-cell effector function. Checkpoint-inhibiting antibodies block this binding. (C) Heavy infiltration of the tumour microenvironment by immunosuppressive myeloid cells (neutrophils and eosinophils) might be involved in resistance to checkpoint blockade, because these cells limit tumour immunity and contrast the activity of immunomodulatory drugs. (D) Immune and inflammatory cell infiltrate in the tumour microenvironment produces molecules that bind proteins expressed on HRS cell membranes. This crosstalk, which shows the biological complexity of the disease, is essential for HRS cell growth and survival. A list of the participating cells and molecules, both those expressed by HRS cells and those produced in the tumour microenvironment, is shown on the right. PD-1=programmed cell death 1. PD-L1=programmed cell death ligand 1. PD-L2=programmed cell death ligand 2. The Lancet 2018 392, 1194-1196DOI: (10.1016/S0140-6736(18)31867-1) Copyright © 2018 Elsevier Ltd Terms and Conditions