Mechanisms of liver-induced tolerance

Abstract

The research during last year offered some key insights into the mechanisms of liver-induced tolerance. Through interactions with activated T cells and B cells via IFN-γ/B7-H1 pathways, liver mesenchymal cells have been shown to be critical components of liver-specific tolerance induction.

Updates and Critical Evaluation on Novel Biomarkers for the Malignant Progression of Intraductal Papillary Mucinous Neoplasms of the Pancreas

“…Recently, it was reported that tumorigenesis in the pancreas is associated with significant intra-and peri-tumoral inflammation and failure of protective immunosurveillance (75). Neutrophil activation and proliferation are indicative of TH-1 pathway of cell-mediated immunity involvement (76). Reasonably, the first phase of inflammation is correlated with increased neutrophil expression, whereas the other 2 phases should be correlated with increased lymphocyte expression (17).…”

“…Thus, despite being non-specific, increased neutrophil-tolymphocyte ratio (NLR) might be indicative of increased active inflammatory process in IPMN-derived malignancies. Peri-pancreatic lymphocyte subsets have divergent effects on tumorigenesis by either suppressing cancer growth via antigen-restricted tumoricidal immune responses (CD8 + T-cells and Th1-polarized CD4 + T-cells) or by promoting tumor progression via induction of immune suppression (myeloid-derived suppressor cells; MDSCs and Th2-deviated CD4 + T-cells) (76,77). Another study showed that pancreatic adenocarcinoma-infiltrating γδ-T cells are a highly influential lymphocyte subset promoting pancreatic oncogenesis and reducing survival via novel cross-talk with the adaptive immune compartment; Nevertheless, they may also have prognostic significance of survival and response to immunotherapeutic regimen (77).…”

Time for hepatocellular carcinoma immunotherapy: insights for successful clinical applications in this challenging tumor

“…Innate immune cells such as natural killer (NK), NKT and γ/δ T cells are found at higher frequency in the liver, as Foxp3+ regulatory T cells (Tregs). The liver environment is also characterized by increased expression of immunosuppressive cytokines such as interleukin (IL)-10 and transforming growth factor (TGF)-β [2] . Hepatocellular carcinoma (HCC) initiation and progression are multi-step processes profoundly influenced by the interplay between hepatocytes and immune cells.…”

CD24 as a Novel Predictive Biomarker in Patients with Hepatocellular Carcinoma: Friend or Foe?

“…First, tolerance could be attributed to continuous exposure to antigens via portal vein, that promotes the expression of a set of cytokines, antigen-presenting molecules and co-stimulatory signals that impose T-cell inactivation, partly via effects on liver antigen presenting cells [12][13][14]. This property facilitates the organ to maintain homeostasis with a concomitant price being paid; that of vulnerability to viral infections, autoimmune diseases and carcinogenesis [15,16]. There is an increasing body of literature supporting the role of cluster of differentiation (CD) 24 as a biomarker for cancer diagnosis and prognosis.…”