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NK Cell Dysfunction and Checkpoint Immunotherapy
Jiacheng Bi1, Zhigang Tian2,3
1Shenzhen Laboratory of Antibody Engineering, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Abstract:
NK cells play important roles in the innate immune responses against tumors. The effector function of NK cells relies on the integration of activating and inhibitory signals. Emerging checkpoint receptors and molecules are being revealed to mediate NK cell dysfunction in the tumor microenvironment. Inhibition of some NK cell surface checkpoint receptors has displayed the potential to reverse NK cell dysfunction in tumors, and to boost anti-tumor immunity, both in clinical trials (anti-KIR and anti-NKG2A), and in preclinical studies (e.g., anti-TIGIT, and anti-CD96). To fully exploit the potential of NK-based checkpoint immunotherapy, more understanding of the regional features of NK cells in the tumor microenvironment is required. This will provide valuable information regarding the dynamic nature of NK cell immune response against tumors, as well as novel checkpoints or pathways to be targeted. In this Review, we discuss recent advances in the understanding of NK cell dysfunction in tumors, as well as emerging strategies of NK-based checkpoint immunotherapy for tumors.
Insights
Natural killer (NK) cells fight tumors but can be suppressed in the tumor microenvironment. Targeting NK cell checkpoints shows promise for boosting anti-tumor immunity.
Area of Science:
- Immunology
- Cancer Research
- Cell Biology
Background:
- Natural killer (NK) cells are crucial for innate anti-tumor immunity.
- NK cell function depends on balancing activating and inhibitory signals.
- The tumor microenvironment often causes NK cell dysfunction via checkpoint receptors.
Purpose of the Study:
- To review recent advances in understanding NK cell dysfunction in tumors.
- To discuss emerging strategies for NK cell-based checkpoint immunotherapy.
- To highlight the need for understanding regional NK cell features in tumors.
Main Methods:
- Literature review of preclinical and clinical studies.
- Analysis of emerging checkpoint receptors and molecules.
- Discussion of therapeutic strategies targeting NK cell checkpoints.
Main Results:
- Several NK cell checkpoint receptors (e.g., KIR, NKG2A, TIGIT, CD96) are implicated in tumor immune evasion.
- Inhibiting specific NK cell checkpoints can reverse dysfunction and enhance anti-tumor responses.
- Clinical and preclinical data support the potential of NK-based immunotherapies.
Conclusions:
- Targeting NK cell checkpoints represents a promising immunotherapy strategy for cancer.
- Further research into the tumor microenvironment's impact on NK cells is needed.
- Identifying novel checkpoints will expand therapeutic options for NK cell-based cancer treatment.
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