RESUMEN
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.
Asunto(s)
Linfocitos B/metabolismo , Carcinoma Hepatocelular/mortalidad , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Hepatitis C/complicaciones , Receptor de Muerte Celular Programada 1/metabolismo , Receptores CCR5/metabolismo , Linfocitos T/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Capecitabina/administración & dosificación , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/virología , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Hepacivirus/aislamiento & purificación , Hepatitis C/virología , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Pronóstico , Sorafenib/administración & dosificación , Tasa de SupervivenciaRESUMEN
UNLABELLED: We studied the level of lipid peroxide, nitric oxide (NO), trace elements (TEs), and microparticles (MPs) in Gaucher disease (GD) before and after 1 year of enzyme replacement therapy (ERT). A total of 15 children with GD and 15 healthy controls were enrolled in this study. Serum level of lipid peroxide, NO, and TEs was determined. The MPs were detected by flow cytometry. The level of lipid peroxide was significantly higher in the patients than in the controls even after ERT. Although NO level was normalized in the patients after ERT, zinc and copper were still lower in the patients after ERT. The percentages of various MPs were significantly higher in the patients than in the controls both before and after ERT. There were positive correlations between chitotriosidase and both lipid peroxide and total MPs. CONCLUSION: The GD is associated with alteration in oxidant and antioxidant status and high level of circulating MPs.