Natural Killer Cells in Liver Disease and Hepatocellular Carcinoma and the NK Cell-Based Immunotherapy

Liu, Pingyi; Chen, Lingling; Zhang, Haiyan

doi:10.1155/2018/1206737

Cited by 103 publications

(91 citation statements)

References 98 publications

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“…The percentage of NK cells among liver cells is five times as high as the percentages among spleen or peripheral blood, suggesting that NK cells may play an important role in the immune function of the liver. Accumulating evidences were found that the NK cells were modulated by liver diseases and were further involved in the pathogenesis of liver injury and inflammation (34). Fucoidan was shown to benefit alcohol and non-alcoholic liver disease (3).…”

Section: Discussionmentioning

confidence: 99%

Activation of NK cells in male cancer survivors by fucoidan extracted from Cladosiphon okamuranus

et al. 2019

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Cancer survivors are highly motivated to seek information about the use of dietary supplements and complementary nutritional therapies to improve their quality of life. Fucoidan, a sulfated polysaccharide extracted from brown marine alga, exhibits a wide range of bioactivities, including anticancer activity. As natural killer (NK) cells serve an important role in defenses against tumor cells, the present study examined the effects of fucoidan extracted from Cladosiphon Okamuranus on NK cell activity in cancer survivors. A prospective, open-label clinical study was conducted on cancer survivors treated with fucoidan via oral administration; 11 cancer survivors with a performance status of 0 or 1 participated and consumed 3 g of fucoidan for 6 months. No significant changes were observed in the mean activities of NK cells in total subjects following the ingestion of fucoidan. An analysis of each sex revealed that NK cell activity was significantly increased by the ingestion of fucoidan in male, yet not female subjects. Serum fucoidan levels were markedly increased following the ingestion of fucoidan and the peak levels ranged between 30 and 198 ng/ml. Tumor markers remained within the reference range during the trial period in subjects, in whom primary tumors were eradicated by treatment. The basal values of tumor markers were elevated in three cases; tumor markers were increased in two cases and decreased in one by the ingestion of fucoidan. These findings suggest that fucoidan enhances the activation of NK cells in male cancer survivors.

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Section: Discussionmentioning

confidence: 99%

Activation of NK cells in male cancer survivors by fucoidan extracted from Cladosiphon okamuranus

et al. 2019

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“…In addition, Cytokine-induced killer (CIK) cells, a heterogeneous cytotoxic immune populations consisting of CD8+ T cells, CD56+ NK cells, and CD3+CD56+ NKT cells, was demonstrated to be safe, with a lower recurrence rate and improved RFS and OS in HCC [183]. NK cell therapy has also been explored for HCC treatment, based on findings that NK cells are dysfunctional in HCC and tumor-infiltration with activated NK cells is associated with superior survival in HCC patients [184,185]. More recently, engineered NK cells or CAR-NK cell therapy with tumor specificity are being explored for various cancer types, including HCC [186].…”

Section: Other Icb Combinationsmentioning

confidence: 99%

Rationale of Immunotherapy in Hepatocellular Carcinoma and Its Potential Biomarkers

Tai

Choo

Chew

2019

Cancers

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Hepatocellular carcinoma (HCC), the most common type of liver cancer, is derived mostly from a background of chronic inflammation. Multiple immunotherapeutic strategies have been evaluated in HCC, with some degree of success, particularly with immune checkpoint blockade (ICB). Despite the initial enthusiasm, treatment benefit is only appreciated in a modest proportion of patients (response rate to single agent ~20%). Therapy-induced immune-related adverse events (irAEs) and economic impact are pertinent considerations with ICB. It is imperative that a deeper understanding of its mechanisms of action either as monotherapy or in combination with other therapeutic agents is needed. We herein discuss the latest developments in the immunotherapeutic approaches for HCC, the potential predictive biomarkers and the rationale for combination therapies. We also outline promising future immunotherapeutic strategies for HCC patients.

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“…59 Dysfunction of other lymphocytes such as the reduced cytotoxicity of NK cells was also reported during chronic hepatitis viral infection. 60 It was previously speculated that NK is more dysfunctional in chronic HBV as compared with chronic HCV infection. 61 However, MICA mutation, which is important for T and NK cells activation, 34,38 was detected in both HBV and HCV-related HCC.…”

Section: Tumor Immune Microenvironmentmentioning

confidence: 99%

“…82 Another ACT using NK cells has also been explored as HCC immunotherapy, based on the rationale that NK cells are dysfunctional in HCC and tumor-infiltration with activated NK cells is associated with superior HCC patient survival. 47,60,83 There is only one complete feasibility and safety study using adoptive NK cells extracted from cadaveric donor liver perfusate for liver transplant recipients with HCC, which demonstrated reduced recurrence rate. 84 Several other NK cell therapy trials in HCC are currently ongoing (clinicaltrials.gov).…”

Section: Other Adoptive Cell Therapiesmentioning

confidence: 99%

Impact of Viral Etiologies on the Development of Novel Immunotherapy for Hepatocellular Carcinoma

Lim

Chew

2019

Semin Liver Dis

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Hepatocellular carcinoma (HCC), is the most common type of liver cancer which is derived mostly from the background of chronic inflammation. Chronic hepatitis viral infection remains one of the most common etiologies implicated in chronic liver inflammation, cirrhosis, and HCC. With such background inflammation, immunotherapy—particularly the checkpoint inhibitors—have been tested in HCC patients with unprecedented success. However, despite the initial enthusiasm, the response rate to immunotherapy remains modest in most clinical trials (approximately 20%), with mixed reports on response rates in hepatitis viral-related HCC as compared with nonviral HCC. Given such complexity in response to immunotherapy, it is increasingly appreciated that deeper understanding of the tumor molecular features and tumor microenvironment of hepatitis viral-related HCC is crucial for the design of more effective immunotherapeutics. We discuss herein the current knowledge in tumor genomic mutational and immune landscapes as well as the ongoing immunotherapy trials in HCC with the unique focus on their viral etiologies. Based on this understanding, we also outline perspectives and rationale on the design of potential immunotherapeutic strategies in HCC patients according to their viral etiologies.

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Natural Killer Cells in Liver Disease and Hepatocellular Carcinoma and the NK Cell-Based Immunotherapy

Cited by 103 publications

References 98 publications

Activation of NK cells in male cancer survivors by fucoidan extracted from Cladosiphon okamuranus

Activation of NK cells in male cancer survivors by fucoidan extracted from Cladosiphon okamuranus

Rationale of Immunotherapy in Hepatocellular Carcinoma and Its Potential Biomarkers

Impact of Viral Etiologies on the Development of Novel Immunotherapy for Hepatocellular Carcinoma

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