Mucosal-associated invariant T (MAIT) cells, defined as CD161 + TCR Vα7.2 + CD3+ T-cells, are a subset of αβ T-cells that possess both innate-and effector-like qualities. 1,2 They are preferentially located in the gut lamina propria and liver 3 and comprise ~1%-10% of the circulating CD3 + T-cells and ~20%-50% of the intrahepatic T-cells in healthy adults. 4,5 MAIT cells play an important role in innate defence against bacterial infections and can be activated by MR1-presented bacterial ligands or by IL-12 and IL-18. 6,7 Chronic hepatitis B virus (CHBV) infection is a noncytopathic infection of host hepatocytes that affects over 240 million people

ObjectiveMucosal-associated invariant T (MAIT) cells are innate T cells with immunoregulatory activity and were recently found to be associated with various tumor types. The role of intrasinusoidal MAIT cells in hepatocellular carcinoma (HCC) has not been fully characterized.DesignPeripheral blood samples were obtained from patients with HCC and healthy controls. Liver-associated mononuclear cells (LMCs) were collected from liver perfusions of donors and patients with HCC undergoing liver transplantation. Blood and liver perfusates from patients with HCC were analyzed by flow cytometry for CD3 +CD161+Vα7.2+MAIT cell frequency, phenotype, and function.ResultsThere were fewer MAIT cells in the peripheral blood and liver of patients with HCC than in the healthy controls. Interferon-γ (IFN-γ) production by these cells was also reduced. Peripheral MAIT cells showed upregulation of HLA-DR (Human Leukocyte Antigen DR） and the inhibitory molecule PD-1 (Programmed Cell Death Protein 1), but no significant differences in upregulation were found in intrasinusoidal MAIT cells. MAIT cells were significantly enriched in the liver relative to that in the peripheral blood of patients with HCC. High levels of activation markers and exhaustion markers including HLA-DR, CD69, and PD-1 were observed in LMCs of patients with HCC but not in the peripheral blood. Single-cell RNA sequencing revealed that intrasinusoidal MAIT cells exhibited distinct features in patients with HCC and the controls.ConclusionOur study showed that alterations in MAIT cells are associated with HCC. The distinct activity and function of MAIT cells in the peripheral blood and liver of patients with HCC might suggest a potential role of these cells in disease pathogenesis.