RESUMO
This systematic review investigates the immunosuppressive environment in HBV-associated hepatocellular carcinoma (HCC), characterized by dysfunctional and exhausted HBV-specific T cells alongside an increased infiltration of HBV-specific CD4+ T cells, particularly regulatory T cells (Tregs). Heightened expression of checkpoint inhibitors, notably PD-1, is linked with disease progression and recurrence, indicating its potential as both a prognostic indicator and a target for immunotherapy. Nevertheless, using PD-1 inhibitors has shown limited effectiveness. In a future perspective, understanding the intricate interplay between innate and adaptive immune responses holds promise for pinpointing predictive biomarkers and crafting novel treatment approaches for HBV-associated HCC.
Assuntos
Imunidade Adaptativa , Carcinoma Hepatocelular , Vírus da Hepatite B , Neoplasias Hepáticas , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/virologia , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/virologia , Vírus da Hepatite B/imunologia , Linfócitos T Reguladores/imunologia , Receptor de Morte Celular Programada 1/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Hepatite B/imunologia , Hepatite B/virologia , Hepatite B/complicações , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Hepatite B Crônica/complicações , Linfócitos T CD4-Positivos/imunologia , Linfócitos T/imunologia , ImunoterapiaRESUMO
Patients with chronic hepatitis B (CHB) gradually develop T cell exhaustion, and the inhibitory receptor molecule, cytotoxic T-lymphocyte antigen-4 (CTLA-4), may play a role in this phenomenon. This systematic review investigates the role of CTLA-4 in the development of T cell exhaustion in CHB. A systematic literature search was conducted on PubMed and Embase on 31 March 2023 to identify relevant studies. Fifteen studies were included in this review. A majority of the studies investigating CD8+ T cells demonstrated increased expression of CTLA-4 in CHB patients, though one study found this only in HBeAg-positive patients. Three out of four studies investigating the expression of CTLA-4 on CD4+ T cells found upregulation of CTLA-4. Several studies showed constitutive expression of CLTA-4 on CD4+ regulatory T cells. CTLA-4 blockade resulted in heterogeneous responses for all T cell types, as it resulted in increased T cell proliferation and/or cytokine production in some studies, while other studies found this only when combining blockade of CTLA-4 with other inhibitory receptors. Although mounting evidence supports a role of CTLA-4 in T cell exhaustion, there is still insufficient documentation to describe the expression and exact role of CTLA-4 in T cell exhaustion in CHB.
