Natural Killer T and Natural Killer Cell-Based Immunotherapy Strategies Targeting Cancer

Area of Science:

• Immunology
• Cancer Biology
• Cellular Therapy

Background:

• Natural killer T (NKT) and natural killer (NK) cells are innate immune cells involved in anti-tumor responses.
• Their function within the tumor microenvironment (TME) is influenced by tumor-derived factors and receptor signaling.
• Dysregulation of NKT and NK cells can impair anti-tumor immunity.

Purpose of the Study:

• To review the current understanding of NKT and NK cell roles in cancer immunity.
• To explore novel therapeutic strategies aimed at mobilizing or restoring NKT and NK cell functions.
• To examine challenges and future directions in NKT and NK cell-based cancer immunotherapies.

Main Methods:

• Literature review of studies investigating NKT and NK cells in the TME.
• Analysis of emerging evidence on bacterial ligands, tumor metabolites, and receptor signaling.
• Examination of recent advancements in NKT and NK cell-based immunotherapies.

Main Results:

• NKT and NK cells exhibit complex roles in the TME, with potential for both anti-tumor and pro-tumor effects.
• Bacterial ligands can activate NKT cells for anti-tumor effects, while tumor metabolites may suppress them.
• Effector memory NKT cells persist in tumor models, and NK cell checkpoint inhibition enhances cytotoxicity.

Conclusions:

• Restoring or enhancing endogenous NKT and NK cell activity is a promising cancer immunotherapy strategy.
• Novel therapies, including CAR-NKT/NK cells and combinations with checkpoint blockade, show potential.
• Further research is needed to overcome challenges and optimize these immunotherapies for clinical success.