The role of PD-1 and PD-L1 in T-cell immune suppression in patients with hematological malignancies

Abstract

T-cell activation and dysfunction relies on direct and modulated receptors. Based on their functional outcome, co-signaling molecules can be divided as co-stimulators and co-inhibitors, which positively and negatively control the priming, growth, differentiation and functional maturation of a T-cell response. We are beginning to understand the power of co-inhibitors in the context of lymphocyte homeostasis and the pathogenesis of leukemia, which involves several newly described co-inhibitory pathways, including the programmed death-1 (PD-1) and PD-1 ligand (PD-L1) pathway. The aim of this review is to summarize the PD-1 and PD-L1 biological functions and their alterative expression in hematological malignancies. The role of PD-1 and PD-L1 in T-cell immune suppression and the potential for immunotherapy via blocking PD-1 and PD-L1 in hematological malignancies are also reviewed.

Figure 1

Schematic structure genomic organization of PD-1 and PD-L1 gene. The bars represent the exons (EX) and the lines represent introns. The blue bars are exons of the PD-1 gene which encode different regions of the PD-1 protein, including: L-region (EX1), hydrophilic-region (EX2), V-likedomain (EX2), connecting-region (EX3), transmembrane-region (EX3), C-like-domain (EX3), intracytoplasmic regions (EX4) and cytoplasmic-region (EX5) [15]. The yellow bars are exons of the PD-L1 gene which encode different regions of the PD-L1 protein, including: Immunoglobulin V-set domain (EX2),immunoglobulin constant domain (EX3), transmembrane region (EX4-EX7); diagonal line filled black and white bar represent the exons which do not express post transcriptional alternative splicing [NM_014143.3]. The numbers under the exons are the number of nucleotides corresponding to size of each exon.