Immune Checkpoint Molecules in Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System

Abstract

Introduction: Primary Diffuse Large B Cell Lymphoma of CNS (PCNSL) is a rare variant of Diffuse Large B Cell Lymphoma (DLBCL) and presents with an aggressive clinical course and usually resistant to commonly used therapy regimens. Recently, role of immune checkpoint molecules including PD-1 and PD-L1 confirmed in some solid tumors and lymphoma resulting tumor cells escape the immune system and help to survive and to spread. Inhibitors of PD-1 and PD-L1 have shown lasting responses in several solid and some hematological tumors, while limited studies evaluate checkpoint molecules on PCNSL. Method: In this study, we investigated PD-1 and PD-L1 expression by immunostaining on 71 patients with PCNSL and correlation with demographic data, location of the tumor, proliferation rate, cell of origin, and CD8 positive T cell infiltration in tumor microenvironment. Results: 16 from 71 showed PD-1 expression, while PD-L1 expression were 42/71. No association was determined between PD-1/PD-L1 expression and gender, cell of origin, and proliferation rate, but a highly significant difference was determined between the infiltration of CD8 positive T cells in two groups of PD-1/PD-L1 positive and negative. Conclusion: This study revealed expression of check point molecules in remarkable number of PCNSL which may open new therapeutic recommendations in this aggressive lymphoma type. Highlights Primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) is a rare variant of Diffuse large B-cell lymphoma limited to the central nervous system. PCNSL has a poor prognosis without response to usual therapy for other types of lymphoma. Checkpoint molecules have a critical role in the pathogenicity of some malignancies. Few research studies have been conducted about the Programmed Death-1 (PD-1) and its ligand PD-L1 (checkpoint molecules) role in the pathogenicity of PCNSL. PD-1 and PD-L1 have been detected in some PCNSLs and show association with T cell infiltration. Plain Language Summary Primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) is a rare variant of high-grade lymphoma of the brain which is limited to immune-privileged organs such as the central nervous system, testis, and eyes. This type of high-grade lymphoma is resistant to usual therapy of other similar lymphomas and shows poor prognosis. Immunotherapy and immune checkpoint (programmed death-1 PD-1 and its ligand PD-L1) inhibitors are new treatment protocols and their use was approved in some solid tumors and few types of lymphoma, including classical Hodgkin lymphoma. However, few research studies have been done on the evaluation of immune checkpoint molecules in the pathogenesis of PCNSL. We investigated these molecules on 71 patients with PCNSL by immunostaining method and noticed the expression of PD-1 and PD-L1 in some of them. This study and similar ones open new therapeutic routes in this aggressive lymphoma type.