Expanded adaptive NKG2C+ NK cells exhibit potent ADCC and functional responses against HBV-infected hepatoma cell...

Area of Science:

• Immunology
• Hepatology
• Cancer Research

Background:

• Hepatitis B virus (HBV) infection causes chronic liver disease and hepatocellular carcinoma (HCC).
• Natural Killer (NK) cells combat HBV-infected cells, but their function declines in chronic infections.
• Adaptive NK cells, marked by NKG2C, offer potential for improved anti-HBV immunity and cancer treatment.

Purpose of the Study:

• To expand and characterize adaptive NK cells from individuals with chronic HBV infection, with or without HIV co-infection.
• To assess the functional capacity of expanded adaptive NK cells against hepatoma cell lines.
• To investigate the potential of TGF-β preconditioning for liver-targeted immunotherapy.

Main Methods:

• Expansion of adaptive NK cells using K562-HLA-E feeder cells and IL-2 from cryopreserved PBMCs.
• Evaluation of NK cell phenotype (NKG2C, CD16, Granzyme B), cytotoxicity, and ADCC.
• Assessment of functional responses against various hepatoma cell lines and autologous T cells.
• TGF-β preconditioning to induce tissue-resident markers (CD103, CD49a).

Main Results:

• Achieved >97% purity and 100-fold expansion of adaptive NK cells with high NKG2C and Granzyme B expression.
• Expanded NK cells demonstrated enhanced ADCC and functional responses against hepatoma cells.
• TGF-β preconditioning induced tissue-resident markers while preserving NK cell function.
• Minimal reactivity against autologous T cells suggests a favorable safety profile.

Conclusions:

• First successful expansion of functional adaptive NK cells from donors with chronic viral infections.
• This approach provides a basis for NK cell-based therapies for HBV functional cure and HCC treatment.
• Combination therapies with monoclonal antibodies may further enhance HBV treatment strategies.