Understanding Immune Evasion and Therapeutic Targeting Associated with PD-1/PD-L1 Pathway in Diffuse Large B-cell Lymphoma

Abstract

In tumor microenvironment, the programmed death 1 (PD-1) immune checkpoint has a crucial role of mechanism of T cell exhaustion leading to tumor evasion. Ligands of PD-1, programmed death ligand 1/2 (PD-L1/L2) are over-expressed in tumor cells and participate in prolonged tumor progression and survivals. Recently, clinical trials for patients who failed to obtain an optimal response prior to standardized chemotherapy in several solid cancers have been focused on targeting therapy against PD-1 to reduce disease progression rates and prolonged survivals. Since various inhibitors targeting the immune checkpoint in PD-1/PD-L1 pathway in solid cancers have been introduced, promising approach using anti-PD-1 antibodies were attempted in several types of hematologic malignances. In diffuse large B cell lymphoma (DLBCL) as the most common and aggressive B cell type of non-Hodgkin’s lymphoma, anti-PD-1 and anti-PD-L1 antibodies were studies in various clinical trials. In this review, we summarized the results of several studies associated with PD-1/PD-L1 pathway as an immune evasion mechanism and described clinical trials about targeting therapy against PD-1/PD-L1 pathway in DLBCL.

High-Throughput MicroRNA Profiling of Vitreoretinal Lymphoma: Vitreous and Serum MicroRNA Profiles Distinct from Uveitis

“…We identified specific miRNA signatures in vitreous and serum associated with VRL, which discriminate VRL from uveitis with vitreous opacity and other controls. These deregulated miRNAs target signaling pathways typically implicated in VRL pathogenesis, such as programmed cell death (PD)-1/PD-L1, WNT/β-catenin, B-cell receptor signaling and nuclear factor-kappa B (NF-κβ) pathway [18][19][20]. Our findings may propose potential biomarkers and a framework for VRL pathogenesis, contribute to the development of new diagnostic biomarkers and guide the next steps of clinical investigations.…”

Immune checkpoints in hematologic malignancies: What made the immune cells and clinicians exhausted!

“…R. Kim et al, 2013;Kiyasu et al, 2015;Kwon et al, 2016;Tavakoli et al, 2019;Thompson et al, 2006;Wahlin et al, 2010). This finding suggests that the expression of PD1 on T cells might be indicative of an active T-cell response against tumor; therefore, PD1 may act as a positive prognostic factor in DLBCL (Carreras et al, 2009;Song et al, 2019;Wahlin et al, 2010). However, this interpretation can be true as long as the majority of PD1 on T cells does not bind to PDL1 on the tumor cell surface.…”

The Tumor Microenvironment of DLBCL in the Computational Era

“…An additional influence of TME on lymphoma behavior involves the defective immune competence of effector cells. A PD-L1 overexpression by tumor and TME components is observable in a considerable fraction of DLBCL showing pools of exhausted PD-1 + T cells (48). The phagocytic activity of Mo and DC is likewise hampered by SIRPα stimulation after binding with CD47, which is up-regulated on tumor cells.…”