The NK cell–cancer cycle: advances and new challenges in NK cell–based immunotherapies

Bald, Tobias; Krummel, Matthew F.; Smyth, Mark J.; Barry, Kevin C.

doi:10.1038/s41590-020-0728-z

Cited by 326 publications

(254 citation statements)

References 212 publications

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“…With advancement of knowledge on NK cell biology, the role of NK cell in tumor immunosurveillance and its clinical implications have been extensively investigated [3]. NK cell could potentially serve as a prognostic factor for patients with GI cancer.…”

Section: Clinical Application Of Nk Cell In Gi Cancermentioning

confidence: 99%

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The role of natural killer cell in gastrointestinal cancer: killer or helper

Wang

Lau

2020

Oncogene

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Gastrointestinal cancer is one of the leading health problems worldwide, with a high morbidity and mortality. To date, harnessing both the innate and adaptive immune system against cancer provides a selective and effective therapeutic strategy for patients. As a first line defense against cancer, natural killer (NK) cells can swiftly target and lyse tumor cells without prior activation. In addition to its pivotal role in innate immunity, NK cells also play unique roles in the adaptive immune system as it enhance anti-tumor adaptive immune responses through secretion of cytokines and retaining an immunological memory. All these characteristics make NK cell a promising anti-cancer agent for patients. In spite of scarce infiltration and impaired function of NK cells in tumors, and the fact that tumors easily develop resistant mechanisms to evade the attacks from endogenous NK cells, multiple strategies have been developed to boost anti-tumor effect of NK cells and abolish tumor resistance. Some examples include adoptive transfer of NK cells after ex vivo activation and expansion; restoration of NK cell function using immune checkpoint inhibitors, and monoclonal antibody or cytokine treatment. Preclinical data have shown encouraging results, suggesting that NK cells hold great potential in cancer therapy. In this review, we discuss NK cells’ cytotoxicity and modulation function in GI cancer and the current application in clinical therapy.

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Section: Clinical Application Of Nk Cell In Gi Cancermentioning

confidence: 99%

“…Nevertheless, it paves way for harnessing the immune system in cancer therapy. In addition to the cytotoxic T lymphocytes, many other immune cell types in both the adaptive and innate immune systems have gained interests in the cancer immunotherapy, among which NK cell is one of the promising candidates [3].…”

Section: Introductionmentioning

confidence: 99%

The role of natural killer cell in gastrointestinal cancer: killer or helper

Wang

Lau

2020

Oncogene

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“…During tumorigenesis, transformed cells can upregulate activating NKG2D ligands (aNKG2DL) as a result of replicative or genotoxic stress 14,17 and can mutate genes in the MHC‐I pathway to evade cytotoxic CD8 + T‐cell recognition 1 . These conditions shift the balance of activating to inhibitory signals in the NK cell–target cell synapse to lead to NK cell‐mediated lysis of tumor cells, which has been extensively reviewed previously 7,12,13,18 . In addition to membrane‐bound tumor ligands, NK cells have also been shown to recognise tumor cells through tumor shed soluble ligands capable of activating NK cells through NKG2D and NKp44 19,20 .…”

Section: Introductionmentioning

confidence: 99%

Arrested development: suppression of NK cell function in the tumor microenvironment

2021

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Natural killer (NK) cells are cytotoxic innate lymphocytes that protect against viral infection and tumor metastasis. Despite their inherent ability to kill a broad range of virally infected, stressed and transformed cells, low numbers of dysfunctional NK cells are often observed in many advanced solid human cancers. Here, we review the potential mechanisms that influence suboptimal mature NK cell recruitment and function in the tumor microenvironment (TME) of solid tumors. We further highlight current immunotherapy approaches aimed to circumvent NK cell dysfunction and discuss next-generation strategies to enhance adoptive NK cell therapy through targeting intrinsic and extrinsic checkpoints the regulate NK cell functionality in the TME. Understanding the mechanisms that drive NK cell dysfunction in the TME will lead to novel immunotherapeutic approaches in the fight against cancer.

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“…Th cells activate T reg lymphocytes [24], inhibit the Th17 cells [25,26], and promote antigen-independent cytotoxicity by inducing the evolution of natural killer (NK) cells into lymphokine-activated killer cells [27][28][29]. The most important actions of Th cells are accomplished by secretion of IL-2, the main growth factor for T lymphocytes [27,30].…”

Section: Anti-inflammatory/immunoregulatory Activity Of Melatoninmentioning

confidence: 99%

Can Melatonin Be a Potential “Silver Bullet” in Treating COVID-19 Patients?

2020

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The therapeutic potential of melatonin as a chronobiotic cytoprotective agent to counteract the consequences of COVID-19 infections has been advocated. Because of its wide-ranging effects as an antioxidant, anti-inflammatory, and immunomodulatory compound, melatonin could be unique in impairing the consequences of SARS-CoV-2 infection. Moreover, indirect evidence points out to a possible antiviral action of melatonin by interfering with SARS-CoV-2/angiotensin-converting enzyme 2 association. Melatonin is also an effective chronobiotic agent to reverse the circadian disruption of social isolation and to control delirium in severely affected patients. As a cytoprotector, melatonin serves to combat several comorbidities such as diabetes, metabolic syndrome, and ischemic and non-ischemic cardiovascular diseases, which aggravate COVID-19 disease. In view of evidence on the occurrence of neurological sequels in COVID-19-infected patients, another putative application of melatonin emerges based on its neuroprotective properties. Since melatonin is an effective means to control cognitive decay in minimal cognitive impairment, its therapeutic significance for the neurological sequels of SARS-CoV-2 infection should be considered. Finally, yet importantly, exogenous melatonin can be an adjuvant capable of augmenting the efficacy of anti-SARS-CoV-2 vaccines. We discuss in this review the experimental evidence suggesting that melatonin is a potential “silver bullet” in the COVID 19 pandemic.

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The NK cell–cancer cycle: advances and new challenges in NK cell–based immunotherapies

Cited by 326 publications

References 212 publications

The role of natural killer cell in gastrointestinal cancer: killer or helper

The role of natural killer cell in gastrointestinal cancer: killer or helper

Arrested development: suppression of NK cell function in the tumor microenvironment

Can Melatonin Be a Potential “Silver Bullet” in Treating COVID-19 Patients?

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