Sleep Deprivation Disturbs Immune Surveillance and Promotes the Progression of Hepatocellular Carcinoma

Huang, Jing; Song, Peiwen; Hang, Kaibin; Chen, Ze-Ka; Zhu, Zidan; Zhang, Yuanjian; Xu, Jinghua; Qin, Jie; Wang, Binghua; Qu, Wei‐Min; Huang, Zhili; Liang, Chao

doi:10.3389/fimmu.2021.727959

Cited by 21 publications

(17 citation statements)

References 45 publications

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“…However, millions of people across the world are sleep-deprived because of sleep-related disorders, lifestyle choices, and so on [ 1 , 2 ]. Sleep disturbances can cause a wide range of disorders throughout the body and lead to increased mortality and morbidity from cardiovascular diseases, cancer, depression, and a series of neurodegenerative diseases [ 3 – 5 ]. Importantly, emerging evidence has demonstrated that cognitive dysfunction is one of the most common and serious consequences induced by sleep loss.…”

Section: Introductionmentioning

confidence: 99%

Involvement of Paired Immunoglobulin-Like Receptor B in Cognitive Dysfunction Through Hippocampal-Dependent Synaptic Plasticity Impairments in Mice Subjected to Chronic Sleep Restriction

Zhai

Gou

et al. 2022

Mol Neurobiol

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Sleep loss is often associated with cognitive dysfunction. Alterations in the structure and function of synapses in the hippocampus are thought to underlie memory storage. Paired immunoglobulin-like receptor B (PirB) plays a negative role in various neurological diseases by inhibiting axon regeneration and synaptic plasticity. However, the contributions of PirB to the mechanisms underlying the changes in synaptic plasticity after sleep loss that ultimately promote deficits in cognitive function have not been well elucidated. Here, we showed that chronic sleep restriction (CSR) mice displayed cognitive impairment and synaptic deficits accompanied by upregulation of PirB expression in the hippocampus. Mechanistically, PirB caused the dysregulation of actin through the RhoA/ROCK2/LIMK1/cofilin signalling pathway, leading to abnormal structural and functional plasticity, which in turn resulted in cognitive dysfunction. PirB knockdown alleviated synaptic deficits and cognitive impairment after CSR by inhibiting the RhoA/ROCK2/LIMK1/cofilin signalling pathway. Moreover, we found that fasudil, a widely used ROCK2 inhibitor, could mimic the beneficial effect of PirB knockdown and ameliorate synaptic deficits and cognitive impairment, further demonstrating that PirB induced cognitive dysfunction after CSR via the RhoA/ROCK2/LIMK1/cofilin signalling pathway. Our study sheds new light on the role of PirB as an important mediator in modulating the dysfunction of synaptic plasticity and cognitive function via the RhoA/ROCK2/LIMK1/cofilin signalling pathway, which indicated that hippocampal PirB is a promising therapeutic target for counteracting cognitive impairment after CSR. Graphical Abstract This illustration depicts the signalling pathway by PirB in mediating cognitive impairment and synaptic deficits in CSR mice. In the hippocampus of CSR mice, the expression level of PirB was significantly increased. In addition, CSR increases RhoA and ROCK2 levels and reduces levels of both LIMK1 and cofilin phosphorylation. PirB knockdown reverses cognitive impairment and synaptic plasticity disorders caused by CSR through the RhoA/ROCK2/LIMK1/cofilin signalling pathway

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Section: Introductionmentioning

confidence: 99%

Involvement of Paired Immunoglobulin-Like Receptor B in Cognitive Dysfunction Through Hippocampal-Dependent Synaptic Plasticity Impairments in Mice Subjected to Chronic Sleep Restriction

Zhai

Gou

et al. 2022

Mol Neurobiol

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“…In the past, multiple studies have found that sleep quality is related to tumor progression, and our previous studies have shown that sleep disorders can impair immunity and promote tumor growth through immune cells in blood and peripheral immune organs in a mouse hepatocellular carcinoma model; however, there is a lack of research in clinical patients with liver cancer [ 18 , 19 ]. This study focuses on two types of patients with HBV cirrhosis and non-HBV cirrhosis.…”

Section: Discussionmentioning

confidence: 99%

Sleep Disturbance Affects Immune Factors in Clinical Liver Cancer Patients

Wang

Huang

et al. 2022

Current Oncology

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Background: Sleep–wake disturbance is prevalent in patients with liver cancer, but there is no direct evidence of its association and related biological mechanisms. Our study was to assess quality of sleep and to describe prevalence of sleep disturbances in patients with different etiologies of liver cancer, especially to explore whether sleep quality influences immune factors. Methods: A total of 210 patients with liver cancer from August 2015 to December 2015 were randomly divided into two groups including HBV cirrhosis and non-HBV cirrhosis. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate their sleep quality, and then 202 patients enrolled in this study were divided into two groups according to their PSQI scores: PSQI ≤ 5 and PSQI > 5. The association between sleep disturbances and immune factors was analyzed by logistic regression models. Results: A total of 56.9% of liver cancer patients experienced poor sleep quality (PSQI > 5). The prevalence of sleep disturbances was significantly higher in patients with liver cancer of non-hepatitis B virus (HBV) cirrhosis than with that evolving from HBV cirrhosis (66.7% vs. 50%, p = 0.018). In non-HBV cirrhosis liver cancer patients, the PSQI > 5 group had a higher percentage of CD3+ T cells (71.06 ± 11.07 vs. 63.96 ± 14.18, p = 0.014) and lower natural killer (NK) cells (14.67 ± 9.65 vs. 20.5 ± 10.77, p = 0.014) compared with patients with PSQI ≤ 5. Logistic regression further confirmed that liver cancer patients without HBV cirrhosis are more prone to experience poor sleep with increased CD3+ T cells (OR = 1.07, 95% CI = 1.01–1.13, p = 0.030) and decreased NK cells (OR = 0.92, 95% CI = 0.85–0.98, p = 0.014). Our results indicate that increased CD3+ T cells and decreased NK cells are both associated with sleep disturbances in patients with liver cancer of non-HBV cirrhosis. Conclusions: Most liver cancer patients suffer from sleep disturbances, especially evolving from non-HBV cirrhosis. A rise in CD3+ T cells and a reduction in NK cells are associated with sleep disturbances in patients with liver cancer of non-HBV cirrhosis.

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“…Tumor cells can down regulate ligands recognized by NK cell receptors through metalloproteinase mediated cleavage and other mechanisms, leading to immune escape ( 40 , 41 ). Second, during tumor development, tumor cells and factors in the tumor microenvironment release a variety of immunosuppressive factors to escape immune surveillance by NK cells ( 42 ). Third, NK cells are inhibited by immunosuppressive cells after immune escape of tumor cells ( 43 ).…”

Section: Nk Cellsmentioning

confidence: 99%

Clinical application and prospect of immune checkpoint inhibitors for CAR-NK cell in tumor immunotherapy

Yang

Zhao²,

Sun³

et al. 2023

Front. Immunol.

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Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells is an attractive research field in tumor immunotherapy. While CAR is genetically engineered to express certain molecules, it retains the intrinsic ability to recognize tumor cells through its own receptors. Additionally, NK cells do not depend on T cell receptors for cytotoxic killing. CAR-NK cells exhibit some differences to CAR-T cells in terms of more precise killing, numerous cell sources, and increased effectiveness in solid tumors. However, some problems still exist with CAR-NK cell therapy, such as cytotoxicity, low transfection efficiency, and storage issues. Immune checkpoints inhibit immune cells from performing their normal killing function, and the clinical application of immune checkpoint inhibitors for cancer treatment has become a key therapeutic strategy. The application of CAR-T cells and immune checkpoint inhibitors is being evaluated in numerous ongoing basic research and clinical studies. Immune checkpoints may affect the function of CAR-NK cell therapy. In this review, we describe the combination of existing CAR-NK cell technology with immune checkpoint therapy and discuss the research of CAR-NK cell technology and future clinical treatments. We also summarize the progress of clinical trials of CAR-NK cells and immune checkpoint therapy.

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Sleep Deprivation Disturbs Immune Surveillance and Promotes the Progression of Hepatocellular Carcinoma

Cited by 21 publications

References 45 publications

Involvement of Paired Immunoglobulin-Like Receptor B in Cognitive Dysfunction Through Hippocampal-Dependent Synaptic Plasticity Impairments in Mice Subjected to Chronic Sleep Restriction

Involvement of Paired Immunoglobulin-Like Receptor B in Cognitive Dysfunction Through Hippocampal-Dependent Synaptic Plasticity Impairments in Mice Subjected to Chronic Sleep Restriction

Sleep Disturbance Affects Immune Factors in Clinical Liver Cancer Patients

Clinical application and prospect of immune checkpoint inhibitors for CAR-NK cell in tumor immunotherapy

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