Department of Clinical Pathology, Faculty of Medicine, Minia University, Minia 61519, Egypt.
J Immunol Res. 2023 Jan 23;2023:4556586. doi: 10.1155/2023/4556586. eCollection 2023.
Many studies have demonstrated that PD-L1/PD-1 signaling is an immune evasion mechanism in tumors. PD-L1/PD-1 coexpression with CXCR3/CD36 in peripheral lymphocytes in lymphoma still needs to be clarified. The current study investigated PD-L1/PD-1 coexpression with CXCR3/CD36 in circulating lymphocytes, serum IL-19 levels, and their correlation with clinical outcome and extranodal involvement in lymphoma. . The coexpression of PD-L1/PD-1 with CXCR3/CD36 on circulating lymphocytes was analyzed by flow cytometry in 78 lymphoma patients before and after therapy and in 50 healthy controls. The concentration levels of IL-19 in serum were assessed by an ELISA. . PD-L1 and PD-1 were expressed on circulating CXCR3+ and CD36+ lymphocytes in lymphoma and were significantly higher in patients with extranodal involvement than in lymphoma patients without extranodal involvement ( < 0.001). Elevated IL-19 levels were observed in lymphoma patients and increased significantly in extranodal involvement ( < 0.001). High percentages of PD-L1+CXCR3+ and PD-1+CXCR3+ lymphocytes were associated with high LDH levels, hepatomegaly, lymphedema, advanced tumor stage, and recurrence. Furthermore, patients with splenomegaly and generalized lymphadenopathy had high percentages of PD-L1+CXCR3+ lymphocytes. In addition, levels of PD-L1/PD-1 coexpression with CXCR3 and IL-19 were significantly associated with bone marrow, lung, and lymph vessel involvement. Further analysis revealed that high percentages of PD-L1+CD36+ and PD-1+CD36+ lymphocytes were associated with lung and bone marrow involvement. Patients with high levels of PD-L1/PD-1 coexpression with CXCR3 and IL-19 had inferior event-free survival (EFS) compared with that in lymphoma patients with low levels. EFS was decreased in patients with high percentages of PD-L1+CD36+ and PD-1+CD36+ lymphocytes. When using the receiver operating characteristic (ROC) curve, the superiority of IL-19 (area under the curve (AUC): 0.993) and PD-L1+CXCR3+% (AUC: 0.961) to PD-1+CXCR3+% (AUC: 0.805), PD-L1+CD36+% (AUC: 0.694), and PD-1+CD36+% (AUC 0.769) was evident in the diagnosis of extranodal involvement, identifying lymphoma patients with extranodal involvement from patients without extranodal involvement. . Coexpression of PD-L1/PD-1 with CXCR3/CD36 in circulating lymphocytes and serum IL-19 levels contributes to poor prognosis and might be potential markers for extranodal involvement in lymphoma.
许多研究表明，PD-L1/PD-1 信号是肿瘤中的一种免疫逃逸机制。淋巴瘤外周血淋巴细胞中 PD-L1/PD-1 与 CXCR3/CD36 的共表达仍需阐明。本研究探讨了循环淋巴细胞中 PD-L1/PD-1 与 CXCR3/CD36 的共表达、血清 IL-19 水平及其与淋巴瘤临床结局和结外累及的相关性。采用流式细胞术检测 78 例淋巴瘤患者治疗前后及 50 例健康对照者循环淋巴细胞中 PD-L1/PD-1 与 CXCR3/CD36 的共表达。采用 ELISA 检测血清 IL-19 浓度水平。结果显示，PD-L1 和 PD-1 在淋巴瘤的循环 CXCR3+和 CD36+淋巴细胞上表达，结外受累患者明显高于无结外受累患者（<0.001）。淋巴瘤患者血清 IL-19 水平升高，结外受累患者明显升高（<0.001）。高百分比的 PD-L1+CXCR3+和 PD-1+CXCR3+淋巴细胞与高 LDH 水平、肝肿大、淋巴水肿、晚期肿瘤分期和复发相关。此外，有脾肿大和全身淋巴结肿大的患者有高百分比的 PD-L1+CXCR3+淋巴细胞。此外，PD-L1/PD-1 与 CXCR3 和 IL-19 的共表达水平与骨髓、肺和淋巴管受累显著相关。进一步分析显示，高百分比的 PD-L1+CD36+和 PD-1+CD36+淋巴细胞与肺和骨髓受累相关。与低水平 PD-L1/PD-1 与 CXCR3 和 IL-19 共表达的淋巴瘤患者相比，高水平 PD-L1/PD-1 与 CXCR3 和 IL-19 共表达的患者无事件生存（EFS）较差。PD-L1+CD36+和 PD-1+CD36+淋巴细胞百分比高的患者 EFS 降低。ROC 曲线显示，IL-19（曲线下面积（AUC）：0.993）和 PD-L1+CXCR3+%（AUC：0.961）优于 PD-1+CXCR3+%（AUC：0.805）、PD-L1+CD36+%（AUC：0.694）和 PD-1+CD36+%（AUC 0.769），可用于诊断结外受累，从无结外受累患者中识别出结外受累的淋巴瘤患者。结论：循环淋巴细胞中 PD-L1/PD-1 与 CXCR3/CD36 的共表达和血清 IL-19 水平与不良预后相关，可能是淋巴瘤结外受累的潜在标志物。
