Diagnostic Performance of PD-L1 versus PD-1 Expression in Circulating CD20 Cells in Diffuse Large B-Cell Lymphoma

Abstract

This study aimed to investigate PD-L1 and PD-1 expression in circulating CD20+ cells in diffuse larger B-cell lymphoma (DLBCL) and to evaluate the predictive and diagnostic performance of PD-L1 versus PD-1 expression in circulating CD20+ cells in DLBCL. Percentages of CD20+, PD-L1+CD20+, and PD-1+CD20+ cells were measured by flow cytometry in 40 DLBCL blood samples and 19 healthy controls. The DLBCL patient group was subdivided into 20 newly diagnosed patients with no treatment yet and 20 patients that had finished six cycles of CHOP therapy. Percentages of PD-L1+CD20+ and PD-1+CD20+ cells were highly significantly increased in pre-therapy patients in comparison to healthy volunteers (p < 0.001). Meanwhile, a significant decrease in percentages of PD-L1+CD20+ and PD-1+CD20+ was observed in post-CHOP therapy patients in comparison to pre-therapy patients (p < 0.001). PD-L1+CD20+ cells were significantly decreased in post-therapy patients when compared to normal controls (p < 0.001), while not for PD-1+CD20+ cells. A strong significant positive correlation between percentages of PD-L1+CD20+ and PD-1+CD20+ was detected in DLBCL patients (p < 0.001). In the pre-therapy group, high PD-L1+CD20+ and PD-1+CD20+ percentages were correlated with serum LDH levels (p = 0.021, p < 0.001). High percentages of PD-1+CD20+ were found in DLBCL patients with splenomegaly (p = 0.027). The results revealed that patients with advanced tumor stages, poor ECOG performance, and non-GCB DLBCL type had increased percentages of PD-L1+CD20+ and PD-1+CD20+ cells. Moreover, PD-L1+CD20+ % and PD-1+CD20+ % were significantly increased in DLBCL patients with bone marrow involvement or B symptoms. The superiority of PD-L1+CD20+ over PD-1+CD20+ was more profound in DLBCL prediction [AUC: 1.0] and in discriminating newly diagnosed patients [AUC: 1.0]. The findings suggest that increased PD-L1/PD-1 expression in peripheral CD20 cells may serve as a companion diagnostic marker for DLBCL. Moreover, percentages of PD-L1+CD20+ cells have better diagnostic performance with higher sensitivity and specificity than PD-1+CD20+ %.

Analysis and identification of oxidative stress-ferroptosis related biomarkers in ischemic stroke

“…Consistently, the biomarkers maintained high AUC values in this validation cohort, further substantiating the robustness of the model and its potential to be generalized across previously unseen data. These observations were consistent with those of previous studies [48][49][50] . www.nature.com/scientificreports/ MAPK8 showed high connectivity in the PPI networks.…”

PD-L1 Is Involved in the Development of Non-Hodgkin’s Lymphoma by Mediating Circulating Lymphocyte Apoptosis

“…The results indicated that NHL patients had immune-function deficiencies in their peripheral blood, suggesting an immune defect. In agreement with previous reports, the study revealed that NHL patients had significantly decreased peripheral immune-cell percentages compared with the healthy controls [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. When the immune system cannot function optimally, T and B cells fail to detect or destroy tumor cells [ 18 , 34 ].…”

“…The findings revealed that immune evasion could be mediated by mechanisms other than tumoral PD-L1 expression. The NHL patients had a significantly greater PD-L1 upregulation in circulating lymphocytes than the healthy controls; this was consistent with a previous study [ 32 ]. The mechanisms behind the PD-L1 increase in circulating immune cells are unknown.…”

“…Fewer circulating PD-1 + cells may be a result of PD-1 loss in exhausted peripheral lymphocytes and fewer malignant cells expressing PD-1. A previous study reported a low expression of PD-1 in circulating CD20 + lymphocytes in DLBCL [ 32 ]. Zhang et al [ 24 ] revealed a high PD-1 expression in CD4 + lymphocytes in DLBCL.…”