image: NK cells express inhibitory receptors (TIGIT, PD-1, NKG2A) that tumors exploit to evade immune attack, alongside activating receptors (NKG2D, DNAM-1) that promote cancer cell killing. Blocking inhibitory checkpoints restores anti-tumor function.
Credit: Anqi Lin, Pengxi Ye, Zhengrui Li, Aimin Jiang, Zaoqu Liu, Quan Cheng, Jian Zhang, and Peng Luo
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."
Method of Research
Literature review
Subject of Research
Not applicable
Article Title
NK Cell Immune Checkpoints and Their Therapeutic Targeting in Cancer Treatment
Article Publication Date
3-Jun-2025
COI Statement
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.