Clinicopathological Study of PD-1/PD-L1 Expression in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) with Emphasis on Large B-Cell Richter Transformation.

Abstract

In the era of immunotherapy, inhibition of the PD-1/PD-L1 immune checkpoint pathway has changed the therapeutic landscape for many tumors. Limited studies were performed on the expression of PD-1 in chronic lymphocytic lymphoma/small lymphocytic lymphoma (CLL/SLL) and its Richter transformation into diffuse large B-cell lymphoma (DLBCL-RT). This study aims to evaluate PD-1/PD-L1 expression and their prognostic role in CLL/SLL, DLBCL-RT, and DLBCL-de novo patients. This retrospective study was conducted on 96 cases (38 CLL/SLL, 11 DLBCL-RT and 47 DLBCL-de novo) that were retrieved from the pathologic and clinical databases at the Oncology Center, Mansoura University. Immunohistochemical evaluation of PD-1 and PD-L1 was assessed in tumor cells and the microenvironment in those patients. This study demonstrated positive expression of PD-1 in CLL/SLL patients, mainly in proliferation centers. Moreover, it showed a higher prevalence of PD-1 expression in DLBCL-RT (9/11 patients) than in DLBCL-de novo (5/47 patients) (P < 0.001). Tumor cells revealed positive PD-L1 expression in 5/47 DLBCL-de novo patients and negative PD-L1 expression in all CLL/SLL and DLBCL-RT patients. PD-1 was positive in reactive T-cells, and PD-L1 was positive in background histiocytes and dendritic cells in all studied cases. PD-1 positive expression in tumor cells was considered an independent poor prognostic factor for overall survival (OS) in DLBCL patients (P = 0.04). In addition, DLBCL-RT had a significantly shorter OS than DLBCL-de novo (P = 0.005). The high prevalence of PD-1 expression in DLBCL-RT patients supports the promising and potential role of anti-PD-1 immunotherapy in the treatment of DLBCL-RT patients.