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Published on: February 22, 2020
The diversity of natural killer cell functional and phenotypic states in cancer
Kumar Rishabh1, Sandro Matosevic2,3
1Department of Industrial and Molecular Pharmaceutics, Purdue University, West Lafayette, IN, USA.
Abstract:
The role of natural killer (NK) cells as immune effectors is well established, as is their utility as immunotherapeutic agents against various cancers. However, NK cells' anti-cancer roles are suppressed in cancer patients by various immunomodulatory mechanisms which alter these cells' identity, function, and potential for immunosurveillance. This manifests in abnormal NK cell responses accompanied by changes in phenotypic or genotypic identity, giving rise to specific NK cell subsets that are either hypofunctional or, more broadly, defective in their responses. Anergy, senescence, and exhaustion are some of the terms that have been used to define and characterize these NK cell functional states. These responses vary not only with cancer type but also NK cell location within tissues. Collectively, these phenomena suggest a highly plastic nature of NK cell biology in tumors. In this review, we present and discuss a summary of these functionally distinct states and provide an overview of how NK cells behave at different locations within the context of cancer.
Insights
Natural killer (NK) cells fight cancer but become suppressed in patients. This review details how NK cell dysfunction, including anergy, senescence, and exhaustion, impacts cancer immunity.
Area of Science:
- Immunology
- Cancer Biology
- Cellular Biology
Background:
- Natural killer (NK) cells are crucial immune effectors and hold promise for cancer immunotherapy.
- Cancer patients exhibit suppressed NK cell anti-tumor activity due to various immunomodulatory mechanisms.
- These mechanisms alter NK cell identity and function, leading to hypofunctional or defective NK cell subsets.
Purpose of the Study:
- To summarize functionally distinct states of NK cells in cancer.
- To provide an overview of NK cell behavior at different tumor locations.
Main Methods:
- Review of current literature on NK cell biology in cancer.
- Analysis of phenotypic and genotypic changes in NK cells.
- Discussion of NK cell functional states like anergy, senescence, and exhaustion.
Main Results:
- NK cell anti-cancer roles are compromised in patients through immunomodulation.
- Dysfunctional NK cell subsets arise, characterized by altered identity, function, anergy, senescence, or exhaustion.
- NK cell responses are plastic and vary by cancer type and tumor location.
Conclusions:
- NK cell biology in tumors is highly plastic, with distinct functional states.
- Understanding these states and locations is key to improving NK cell-based cancer immunotherapies.
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