About this Research Topic
Cancer immunotherapy has become a standard of care in the treatment of a number of malignant diseases. Natural killer (NK) cells have shown to play a critical role, though still poorly defined, in the process by which the immune system controls cancer progression. Indeed, there is strong evidence for the significance of NK cells in the control of cancer cells and thus, NK cell-based therapy has been explored in a number of cancers. However, NK cell activation is highly regulated to prevent an exacerbated immune response by self-regulatory mechanisms that involve exhaustion, anergy and/or senescence, among others, mechanisms that can be exploited by cancer cells to facilitate immune escape. These factors likely explain why NK cell-based therapy clinical outcomes have been rather disappointing. Therefore, a better understanding of the mechanisms involving NK cell regulation which consequently cause NK cell dysfunction during cancer progression are still needed to enhance NK cell-dependent anti-tumor efficacy.
Despite the tremendous progress in cancer immunotherapy, the number of patients benefiting from this type of treatment are still in the minority. Tumor heterogeneity and tumor immune escape mechanisms as well as intrinsic immune regulation are important contributing factors to the failure of immunotherapy. Importantly, NK cell dysfunction is a frequent observation in cancer patients before, during, and/or after treatment. However, how and why NK cell dysfunction occurs is still unknown. Limited studies have suggested that sustained stimulation during cancer treatment causes NK cell exhaustion contributing to NK cell dysfunction; similar to what has been observed during chronic infections; and, thus negatively impacting the cancer therapy outcome. However, the functional and phenotypic features of NK cell exhaustion are still ill-defined and it has been challenging to separate this process from others like anergy and senescence. Additionally, the role of checkpoint inhibitors in these processes is still unclear. Therefore, a better understanding on the complexity of the regulation of NK cell function during cancer progression and treatment is needed to fully realize the potential of NK cell-based therapies.
This Research Topic aims to provide a comprehensive overview of recent advances in the understanding of the regulation of NK cell activation and function that affects its ability to fight cancer as well as therapeutic interventions that result in better NK cell-mediated anti-tumor responses. We encourage submission of original research articles, reviews, mini reviews and perspective articles to cover aspects relevant to NK cell dysfunction and NK cell-based therapies, including, but not limited to:
1. Phenotypic and functional characterization of NK cell exhaustion, anergy and/or senescence
2. Regulatory mechanisms of NK cell dysfunction
3. Therapeutic interventions that target NK cell exhaustion/anergy/senescence and prevent NK cell dysfunction.
4. Role of checkpoint inhibitors in NK cell exhaustion/anergy/senescence
5. Impact of NK cell exhaustion/anergy/senescence in cancer progression
6. Impact of NK cell exhaustion/anergy/senescence in cancer treatment
Keywords: NK Cell exhaustion, anergy, senescence, immunotherapy, NK cell-based therapy
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