A comprehensive analysis published in Reserch illuminates how cancer cells hijack immune checkpoints on natural killer (NK) cells to disable the body’s frontline defense system. The study details:
Dual Checkpoint Categories: Tumor cells exploit both surface receptors (e.g., TIGIT, NKG2A, PD-1) and intracellular molecules (e.g., BIM, EZH2) to paralyze NK cell killing, cytokine secretion, and proliferation.
Breakthrough Therapeutics: Anti-TIGIT antibodies (tiragolumab/vibostolimab) combined with PD-1 inhibitors doubled progression-free survival in liver cancer trials. CRISPR-edited NK cells lacking NKG2A showed 80% higher tumor-killing efficiency.
CAR-NK Innovation: NK cells engineered with chimeric antigen receptors (CARs) targeting TIM-3 or NKG2D eliminated acute myeloid leukemia cells with no graft-versus-host disease risk.
Clinical Urgency: NK cell dysfunction correlates with poor prognosis in lung, liver, and colorectal cancers. Restoring NK activity via checkpoint blockade converted "cold" tumors to "hot" immunogenic environments.
"Targeting NK checkpoints is a paradigm shift," said co-corresponding author Dr. Peng Luo. "Unlike T-cell therapies, NK-based strategies offer ‘off-the-shelf’ potential with fewer side effects."
Literature review
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NK Cell Immune Checkpoints and Their Therapeutic Targeting in Cancer Treatment
3-Jun-2025
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.