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natural killer cell hepatocellular carcinoma

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https://www.readbyqxmd.com/read/29163709/the-anti-hepatocellular-carcinoma-activity-of-mel-p15-is-mediated-by-natural-killer-cells
#1
Tao Xu, Tongxing Cui, Lipan Peng, Shuai Kong, Jianqiang Zou, Xingsong Tian
Mel-P15 is a peptide derived from melittin, the main toxic component in the venom of the European honeybee Apis mellifera. In the present study, the antitumor effects of Mel-P15 and the underlying molecular mechanisms of these effects in vivo were investigated. Mel-P15 directly stimulated natural killer (NK) cell cytotoxicity in vitro, which was increased to 55.45% at a 4 µg/ml dose of Mel-P15. In the mouse liver cancer (H22) xenograft mice model, Mel-P15 suppressed tumor growth in vivo; the tumor inhibitory rate was 61...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29156047/immunopathogenesis-of-hepatitis-b-virus
#2
Tai-Chung Tseng, Li-Rung Huang
Chronic hepatitis B virus (HBV) infection is a global public health issue. There are >250 million people chronically infected with HBV, and these chronic carriers are at high risk of developing end-stage liver diseases and hepatocellular carcinoma. Patients with chronic hepatitis B (CHB) usually acquire the virus perinatally, while most patients infected during adulthood develop acute hepatitis B (AHB), which usually results in viral clearance. HBV infection is noncytopathic, and liver injury is mostly contributed by host immune responses...
November 16, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29149205/kir-content-genotypes-associate-with-carriage-of-hepatitis-b-surface-antigen-e-antigen-and-hbv-viral-load-in-gambians
#3
Louis-Marie Yindom, Maimuna Mendy, Christopher Bodimeade, Caroline Chambion, Peter Aka, Hilton C Whittle, Sarah L Rowland-Jones, Robert Walton
BACKGROUND: Hepatocellular carcinoma (HCC) causes over 800,000 deaths worldwide annually, mainly in low income countries, and incidence is rising rapidly in the developed world with the spread of hepatitis B (HBV) and C (HCV) viruses. Natural Killer (NK) cells protect against viral infections and tumours by killing abnormal cells recognised by Killer-cell Immunoglobulin-like Receptors (KIR). Thus genes and haplotypes encoding these receptors may be important in determining both outcome of initial hepatitis infection and subsequent chronic liver disease and tumour formation...
2017: PloS One
https://www.readbyqxmd.com/read/29115974/stat3-blocked-whole-cell-hepatoma-vaccine-induces-cellular-and-humoral-immune-response-against-hcc
#4
Qiuju Han, Yaqun Wang, Min Pang, Jian Zhang
BACKGROUND: Whole-cell tumor vaccines have shown much promise; however, only limited success has been achieved for the goal of eliciting robust tumor-specific T-cell responses. METHODS: Hepatocellular carcinoma (HCC) cells, H22 and Hepa1-6, were modified by blocking the STAT3 signaling pathway with a STAT3 decoy oligodeoxynucleotide, and the immunogenicity and possibility of using these cell lysates as a vaccine were evaluated. RESULTS: STAT3-blocked whole HCC cell lysates inhibited tumor growth and tumorigenesis, and prolonged the survival of tumor-bearing mice...
November 7, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28962171/role-of-natural-killer-cells-in-liver-transplantation-treatment-of-liver-cancer
#5
Wenbin Ji, Jin Chen, Yuche Mi, Guiliang Wang, Xinjiang Xu, Weizheng Wang
Liver cancer caused by diet or life style is a significant public health problem. Liver transplantation (LT) is a commonly used method of treatment for the liver cancer. The present study aimed to determine whether assessing the net state of natural killer (NK) cell function following LT distinguishes patients at risk for transplantation rejection. A total of 53 patients were involved; all underwent LT for hepatocellular carcinoma with (n=13) or without (n=40) transplantation rejection. The density of interferon-γ (IFN-γ) in blood serum was examined and patients were divided into two groups: Higher (H) and lower (L), on the basis of IFN-γ density...
September 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28871002/trichostatin-a-sensitizes-hepatocellular-carcinoma-cells-to-enhanced-nk-cell-mediated-killing-by-regulating-immune-related-genes
#6
Sangsu Shin, Miok Kim, Seon-Jin Lee, Kang-Seo Park, Chang Hoon Lee
BACKGROUND/AIM: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. The ability of HCC to avoid immune detection is considered one of the main factors making it difficult to cure. Abnormal histone deacetylation is thought to be one of the mechanisms for HCC immune escape, making histone deacetylases (HDACs) attractive targets for HCC treatment. Here, we investigated the effect of trichostatin A (TSA), a highly potent HDAC inhibitor, on HCC (HepG2) gene expression and function...
September 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/28780700/natural-killer-cells-in-hepatocellular-carcinoma-current-status-and-perspectives-for-future-immunotherapeutic-approaches
#7
REVIEW
Min Yu, Zonghai Li
Hepatocellular carcinoma (HCC) is currently the fifth most common malignancy and the third leading cause of cancer-related mortalities worldwide. In the last few years, treatments for HCC have significantly improved from a mere surgical resection to a series of minimally invasive therapies and targeted drugs. However, recurrence frequently occurs even upon curative therapeutics, and drug therapies generally produce disappointing results, with the overall prognosis dismal. This challenging clinical scenario warrants new effective and life-prolonging strategies for patients with HCC...
August 5, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28747084/mir-615-5p-depresses-natural-killer-cells-cytotoxicity-through-repressing-igf-1r-in-hepatocellular-carcinoma-patients
#8
Mai Atef Rahmoon, Rana Ahmed Youness, Asmaa Ibrahim Gomaa, Mohamed Tarif Hamza, Imam Waked, Hend Mohamed El Tayebi, Ahmed Ihab Abdelaziz
miR-615-5p was characterized by our group as a tumour suppressor. IGF-1 R activates a downstream signalling pathway, well characterized in liver cells, however, its role in immunity especially Natural Killer cells (NKs) remains vague. This study aimed at investigating the regulatory role of miR-615-5p on IGF signalling and its impact on NKs cytotoxicity in HCC. Our results showed an upregulation in miR-615-5p and IGF-1 R in NKs of 130 HCC patients compared to 35 controls. Forcing the expression of miR-615-5p, repressed IGF-IR, attenuated NKs cytotoxicity, decreased CD56(dim), increased CD56(bright) NK subsets and reduced the cytotoxic markers NKG2D, TNF-α and perforins...
July 27, 2017: Growth Factors
https://www.readbyqxmd.com/read/28674001/delineation-of-an-immunosuppressive-gradient-in-hepatocellular-carcinoma-using-high-dimensional-proteomic-and-transcriptomic-analyses
#9
Valerie Chew, Liyun Lai, Lu Pan, Chun Jye Lim, Juntao Li, Raymond Ong, Camillus Chua, Jing Yao Leong, Kiat Hon Lim, Han Chong Toh, Ser Yee Lee, Chung Yip Chan, Brian K P Goh, Alexander Chung, Pierce K H Chow, Salvatore Albani
The recent development of immunotherapy as a cancer treatment has proved effective over recent years, but the precise dynamics between the tumor microenvironment (TME), nontumor microenvironment (NTME), and the systemic immune system remain elusive. Here, we interrogated these compartments in hepatocellular carcinoma (HCC) using high-dimensional proteomic and transcriptomic analyses. By time-of-flight mass cytometry, we found that the TME was enriched in regulatory T cells (Tregs), tissue resident memory CD8(+) T cells (TRMs), resident natural killer cells (NKRs), and tumor-associated macrophages (TAMs)...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28617830/on-treatment-decrease-of-nkg2d-correlates-to-early-emergence-of-clinically-evident-hepatocellular-carcinoma-after-interferon-free-therapy-for-chronic-hepatitis-c
#10
Po-Sung Chu, Nobuhiro Nakamoto, Nobuhito Taniki, Keisuke Ojiro, Takeru Amiya, Yuko Makita, Hiroko Murata, Akihiro Yamaguchi, Shunsuke Shiba, Rei Miyake, Tadashi Katayama, Aya Ugamura, Akihiko Ikura, Karin Takeda, Hirotoshi Ebinuma, Hidetsugu Saito, Takanori Kanai
BACKGROUND AND AIMS: Interferon (IFN)- free direct antiviral agents (DAAs) with rapid HCV eradication might evoke immunological reconstitutions, and some early recurrences of HCC after IFN-free DAAs have been reported. This study aimed to investigate whether natural killer group 2, member D (NKG2D) predicts early emergence of HCC after IFN-free DAAs. METHODS: We conducted a clinical practice-based observational study of 101 patients infected with genotype 1 HCV who received IFN-free (DAAs), and stratified them into those who did or did not develop early (i...
2017: PloS One
https://www.readbyqxmd.com/read/28593566/cellular-and-molecular-targets-for-the-immunotherapy-of-hepatocellular-carcinoma
#11
REVIEW
Vikrant Rai, Joe Abdo, Abdullah N Alsuwaidan, Swati Agrawal, Poonam Sharma, Devendra K Agrawal
Liver cancer is the sixth most common cancer worldwide and 3rd most common cause of cancer-related death. Hepatocellular carcinoma (HCC) represents more than 90% of primary liver cancer and is a major public health problem. Due to the advanced stages of HCC at the time of diagnosis, utilizing the conventional treatment for solid tumors frequently ends with treatment failure, recurrence, or poor survival. HCC is highly refractory to chemotherapy and other systemic treatments, and locoregional therapies or selective internal radiation therapies are largely palliative...
June 7, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28567042/hepatitis-c-virus-and-human-cytomegalovirus-natural-killer-cell-subsets-in-persistent-viral-infections
#12
REVIEW
Julia Pollmann, Alexander Rölle, Maike Hofmann, Adelheid Cerwenka
Hepatitis C virus (HCV) and human cytomegalovirus (HCMV) are prominent examples of RNA and DNA viruses, respectively, that establish a persistent infection in their host. HCV affects over 185 million patients worldwide, who are at high risk for developing liver fibrosis, liver cirrhosis, and ultimately hepatocellular carcinoma. Recent breakthroughs in HCV therapy, using direct-acting antivirals have provided the opportunity to monitor natural killer (NK) cells after clearance of a chronic infection. There is now increasing evidence that the individual NK cell repertoire before infection is predictive for the course of disease...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28550492/microrna-889-is-downregulated-by-histone-deacetylase-inhibitors-and-confers-resistance-to-natural-killer-cytotoxicity-in-hepatocellular-carcinoma-cells
#13
Haitao Xie, Qiugui Zhang, Hui Zhou, Jun Zhou, Ji Zhang, Yan Jiang, Jinghong Wang, Xianglin Meng, Leping Zeng, Xiaoxin Jiang
Major histocompatibility complex class I chain-related gene B (MICB) is expressed on tumor cells and participates in natural killer (NK) cell-mediated antitumor immune response through engagement with the NKG2D receptor. This study was undertaken to identify novel microRNA (miRNA) regulators of MICB and clarify their functions in NK cell-mediated cytotoxicity to hepatocellular carcinoma (HCC) cells. Bioinformatic analysis and luciferase reporter assay were conducted to search for MICB-targeting miRNAs. Overexpression and knockdown experiments were performed to determine the roles of candidate miRNAs in the susceptibility of HCC cells to NK lysis...
May 26, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28529568/a-different-representation-of-natural-t-cells-and-natural-killer-cells-between-tumor-infiltrating-and-periphery-lymphocytes-in-human-hepatocellular-carcinoma
#14
Xiao-Feng Li, Dong Dai, Xiu-Yu Song, Jian-Jing Liu, Lei Zhu, Xiang Zhu, Wenchao Ma, Wengui Xu
Natural T cells [cluster of differentiation (CD) 3(+)CD56(+)] and natural killer (NK) cells (CD3(-)CD56(+)) are particularly abundant in the human liver and serve an important role in immune responses in the liver. The aim of the present study was to extensively determine the phenotypic and functional characteristics of natural T and NK cells in human hepatocellular carcinoma (HCC). Tumorous and non-tumorous tissue infiltrating lymphocytes (TILs and NILs, respectively) and peripheral blood mononuclear cells (PBMCs) from patients with hepatocellular carcinoma (HCC) were obtained to determine the frequency and phenotype of natural T/NK cells by a multicolor fluorescence activated cell sorting analysis...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28507442/aberrant-promoter-methylation-profiles-and-association-with-survival-in-patients-with-hepatocellular-carcinoma
#15
Dani Zhong, Hong Cen
The aim of this study was to investigate the prognostic and diagnostic value of genes with promoter methylation in hepatocellular carcinoma (HCC) patients. On the basis of The Cancer Genome Atlas data, we identified genes with differentially methylated promoters in HCC tissues and adjacent non-tumor tissues, using the linear models for microarray data approach. Cox proportional hazard regression analysis was applied to access the prognostic value of identified differentially methylated genes. The diagnostic value of the genes was evaluated through receiver operating characteristic...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28468916/tumor-derived-%C3%AE-fetoprotein-directly-drives-human-natural-killer-cell-activation-and-subsequent-cell-death
#16
Lazar Vujanovic, Elizabeth C Stahl, Angela D Pardee, David A Geller, Allan Tsung, Simon C Watkins, Gregory A Gibson, Walter J Storkus, Lisa H Butterfield
Hepatocellular carcinoma (HCC) patients with reduced natural killer (NK)-cell numbers and function have been shown to have a poor disease outcome. Mechanisms underlying NK-cell deficiency and dysfunction in HCC patients remain largely unresolved. α-Fetoprotein (AFP) is an oncofetal antigen produced by HCC. Previous studies demonstrated that tumor-derived AFP (tAFP) can indirectly impair NK-cell activity by suppressing dendritic cell function. However, a direct tAFP effect on NK cells remains unexplored. The purpose of this study was to examine the ability of cord blood-derived AFP (nAFP) and that of tAFP to directly modulate human NK-cell activity and longevity in vitro Short-term exposure to tAFP and, especially, nAFP proteins induced a unique proinflammatory, IL2-hyperresponsive phenotype in NK cells as measured by IL1β, IL6, and TNF secretion, CD69 upregulation, and enhanced tumor cell killing...
June 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28448867/immuno-modulatory-and-cellular-antioxidant-activities-of-%C3%AE%C2%BA-selenocarrageenan-in-combination-with-epirubicin-in-h22-hepatoma-bearing-mice
#17
Na Ling, Xiaojun Zhou, Yubin Ji, Wenlan Li, Chenfeng Ji, Zheng Qi
BACKGROUND: Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival time. The aim of this study is to evaluate the synergistic anti-tumor effects and underlying mechanism of κ-selenocarrageenan (KSC) in combination with the chemotherapy drug epirubicin (EPI) in H22 tumor-bearing mice. METHODS: Hepatocellular carcinoma H22 cells were implanted into mice. After the transplants were successfully established, the animals were divided into four groups: namely the control group, the KSC group, the EPI group and the KSC+EPI group...
July 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28428708/indoleamine-2-3-dioxygenase-as-a-potential-prognostic-marker-and-immunotherapeutic-target-for-hepatocellular-carcinoma
#18
REVIEW
Kashif Asghar, Asim Farooq, Bilal Zulfiqar, Muhammad Usman Rashid
Tumor cells induce an immunosuppressive microenvironment which leads towards tumor immune escape. Understanding the intricacy of immunomodulation by tumor cells is essential for immunotherapy. Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme which mediates tumor immune escape in various cancers including hepatocellular carcinoma (HCC). IDO up-regulation in HCC may lead to recruitment of regulatory T-cells into tumor microenvironment and therefore inhibit local immune responses and promote metastasis...
April 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28428075/immunotherapy-of-hepatocellular-carcinoma-using-chimeric-antigen-receptors-and-bispecific-antibodies
#19
REVIEW
Sayed Shahabuddin Hoseini, Nai-Kong V Cheung
Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide with an overall survival rate of less than 15% in developed countries. Despite attempts at new therapeutic strategies, the majority of patients succumb to this cancer. Buttressed by the highly successful clinical impact in melanoma, immunotherapy is gaining momentum as the next treatment modality for many human cancers. Chimeric antigen receptors (CAR) contain the antigen binding moieties of a monoclonal antibody and the co-stimulatory and signaling domains associated with effector receptor signaling...
July 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28287817/liver-metastasis-from-neuroendocrine-carcinoma-after-the-use-of-the-new-direct-action-antivirals-against-hepatitis-c-virus-in-a-patient-with-past-history-of-hepatocellular-carcinoma
#20
María Caldas Álvarez, Lourdes Del Campo, Alwalid Freih-Fraih, Luisa García-Buey
The use of the new direct-action antivirals against hepatitis C virus provides very high viral eradication rates. However, various recently published articles recommend caution with their use after the appearance of some cases of de novo tumors (originated in hepatic and extra-hepatic locations) and a possible shorter time period of recurrence of hepatocellular carcinomas previously treated with surgery or loco-regional therapies. The sudden drop of the number of natural killer cells secondary to the use of these new medicines has been suggested as one of the possible mechanisms responsible for this process...
March 13, 2017: Revista Española de Enfermedades Digestivas
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