Different aberrant expression pattern of immune checkpoint receptor in patients with T-NHL and NK/T-CL

Abstract

T-cell immunodeficiency plays a crucial role in the development and progression of tumor. Immune checkpoint (co-inhibitory receptors) and TCR signal pathway regulate T-cell function in opposite way. Our previous study showed the decreasing trend in T cell activation related TCR signal pathway expression in peripheral blood mononuclear cells (PBMCs) from T-cell non-Hodgkin lymphomas (T-NHL) and NK/T-cell lymphoma (NK/T-CL). However, how immunosuppression status regulated by the co-inhibitory receptors, like programmed death 1 (PD-1), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), B/T lymphocyte attenuator (BTLA) expanded to Lymphocyte-activation gene 3 (LAG-3), T cell immunoglobulin-3 (TIM-3), T cell immunoglobulin and ITIM domain (TIGIT) remains unclear. In this study, we characterized the expression pattern of all these immunosuppressive receptors in PBMCs form T-NHL and NK/T-CL patient by real-time qPCR. Significantly higher PD-1 expression level was detected in both T-NHL (n=14) and NK/T-CL (n=8) when compare to HI (healthy individuals, n=22,), while the expression level of its ligand PD-L1 had no statistic difference in both groups in comparison to HI group. The expression of BTLA, LAG-3, TIM-3, ICOS and TIGIT significantly increased in T-NHL group, but not in NK/T-CL group. While higher expression of CTLA-4 was found only in NK/T-CL group. When disease stage was considered in, BTLA is only up-regulating in advanced stage (stage III and IV), most patients with high ICOS expression level are in stage I and II. Moreover, the positive correlation between the expression level of LAG-3, TIM3 and TIGIT gene in HI group was impacted when it comes to either T-NHL or NK/T-CL patients. In conclusions, aberrant expression pattern of T-lymphocyte inhibitory receptors is a common characteristic in patients with T- NHL or NK/T-CL, which is one of reasons of immunosuppression, moreover, the different upregulating of such inhibitory receptors between T-NHL and NK/T-CL might be as immune biomarkers for evaluation the immunosuppression status and help to establish the precision target of immunotherapy.