Differential expression of Tim-3, PD-1, and CCR5 on peripheral T and B lymphocytes in hepatitis C virus-related hepatocellular carcinoma and their impact on treatment outcomes

Abstract

Background and objective Activation of the immune checkpoints and expression of chemokines and chemokine receptors have been reported to promote HCC progression. This study aimed to assess the differential expression of Tim-3, PD-1, and CCR5 on peripheral blood lymphocytes from patients with HCV-related HCC and correlate their expression with the treatment outcomes. Patients and methods The study incorporated 40 patients with chronic HCV-related HCC and 40 healthy controls. Patients were radiologically assessed for hepatic focal lesions and portal vein thrombosis. Response to HCC treatment and overall survival (OS) outcomes were determined. The expression of Tim-3, PD-1, and CCR5 among CD19(+), CD4(+), and CD8(+)lymphocytes was assessed by flow cytometry. Results Higher frequencies of CD4(+)and CD8(+)cells expressing each of Tim-3 and PD-1 and PD-1(+)CD19(+)cells were observed in the HCV-related HCC patients in comparison with controls.The highest expression of Tim-3 and PD-1 was by the CD8(+)cells.Strong relations were detected among PD-1(+)CD19(+), PD-1(+)CD4(+)and PD-1(+)CD8(+)cells. Elevated levels of PD-1(+)lymphocytes were significantly associated with poor treatment response and shorter OS. Conclusion Modulation of the expression of immune checkpoints as Tim-3 and PD-1, and of CCR5 on T cells is somehow related to HCC. CD8(+)T cells expressing PD-1 were the most relevant to HCC prognosis (OS and treatment response) and could represent a promising target for immune therapy against HCC. Future studies need to focus on exploring PD-1(+)B cells and Tim-3(+)CD4(+)cells, which seem to play a significant role in the pathogenesis of HCC.