Ultrasound-guided radiofrequency ablation enhances natural killer-mediated antitumor immunity against liver cancer

Mo, Zelai; Lu, Hailan; Mo, Shaowei; Fu, Xiangmin; Chang, Shunwu; Yue, Jie

doi:10.3892/ol.2018.8231

Cited by 10 publications

(10 citation statements)

References 44 publications

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“…Radiofrequency ablation (RFA) is an effective and low risk treatment for hepatocellular carcinoma, and is especially suitable for patients with liver cancer, which are not suitable for operation. A total of five New Zealand white rabbits aged between two to three months, weighing 2.5-3.0 kg were randomly selected and established as an animal model of hepatocellular carcinoma in the novel studies of Mo et al [69]. Two weeks later, the expression level of NKG2D receptors on NK cells in the white rabbits were all detected by flow cytometry and the levels of IFN-γ and TNF-α were tested by ELISA on basis of hematoxylin and eosin (H&E) staining of the liver tissue on the slices.…”

Section: Tnf-alpha Secreted By Nk Cells Exerts Anti-hepatocarcinoma Amentioning

confidence: 99%

Recent Advances in Molecular Mechanisms of the NKG2D Pathway in Hepatocellular Carcinoma

Wang¹,

Li²,

Sun³

2020

Biomolecules

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Hepatocellular carcinoma is a common malignant tumor with high mortality. Its malignant proliferation, invasion, and metastasis are closely related to the cellular immune function of the patients. NKG2D is a key activated and type II membrane protein molecule expressed on the surface of almost all NK cells. The human NKG2D gene is 270 kb long, located at 12p12.3–p13.1, and contains 10 exons and 9 introns. The three-dimensional structure of the NKG2D monomeric protein contains two alpha-helices, two beta-lamellae, and four disulfide bonds, and its’ signal of activation is transmitted mainly by the adaptor protein (DAP). NKG2D ligands, including MICA, MICB, and ULBPs, can be widely expressed in hepatoma cells. After a combination of NKG2D and DAP10 in the form of homologous two polymers, the YxxM motif in the cytoplasm is phosphorylated and then signaling pathways are also gradually activated, such as PI3K, PLCγ2, JNK-cJunN, and others. Activated NK cells can enhance the sensitivity to hepatoma cells and specifically dissolve by releasing a variety of cytokines (TNF-α and IFN-γ), perforin, and high expression of FasL, CD16, and TRAIL. NK cells may specifically bind to the over-expressed MICA, MICB, and ULBPs of hepatocellular carcinoma cells through the surface activating receptor NKG2D, which can help to accurately identify hepatoma, play a critical role in anti-hepatoma via the pathway of cytotoxic effects, and obviously delay the poor progress of hepatocellular carcinoma.

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Section: Tnf-alpha Secreted By Nk Cells Exerts Anti-hepatocarcinoma Amentioning

confidence: 99%

Recent Advances in Molecular Mechanisms of the NKG2D Pathway in Hepatocellular Carcinoma

Wang¹,

Li²,

Sun³

2020

Biomolecules

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“…At present, recurrence and metastasis are key factors that limit clinical outcomes of HCC patients [3]. Immune escape is also an important prerequisite for tumor recurrence and metastasis [19]. NK cells are important cells in the innate immune system, and they can quickly identify and kill tumor cells [18, 20].…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-inducible gene 2 promotes the immune escape of hepatocellular carcinoma from nature killer cells through the interleukin-10-STAT3 signaling pathway

Cui

Yang

et al. 2019

J Exp Clin Cancer Res

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Background The study examines the expression and function of hypoxia-inducible gene 2 (HIG2) in hepatocellular carcinoma (HCC) tissues and cells. Methods Forty patients with HCC were included in the study. Bioinformatic analysis was used to analyze the clinical relevance of HIG2 expression in HCC tissue samples. Immunohistochemistry was employed to determine the expression of target proteins in tumor tissues. Hepatic HepG2 and SMMC-7721 cells were transfected with HIG2 -targeting siRNA with Lipofectamine 2000. qRT-PCR was carried out to determine gene expression levels, while Western blotting was used to determine protein expression. A CCK-8 assay was performed to detect proliferation of cells, while migration and invasion of cells were studied by Transwell assay. Flow cytometry was carried out to detect surface markers and effector molecules in Nature killercells, as well as the killing effect of NK cells. Results HIG2 expression was upregulated in HCC. Silencing of HIG2 suppressed HCC cell migration and invasion. The killing effect of NK cells on HCC cells was enhanced after HIG2 was silenced in HCC cells. Conditioned media from HIG2 -silenced SMMC-7721 cells inhibited the phenotype and function of NK cells. HCC cells with silenced expression of HIG2 modulated the activity of NK cells via STAT3. HIG2 promoted the evasion of HCC cells from killing by NK cells through upregulation of IL-10 expression. Conclusion The study demonstrates that HIG2 activates the STAT3 signaling pathway in NK cells by promoting IL-10 release by HCC cells, thereby inhibiting the killing activity of NK cells, and subsequently promoting the recurrence and metastasis of HCC.

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“…RFA causes protein denaturation and coagulative necrosis by heating, and blocks the blood supply to the tumor, further causing tumor cell ischemia and delaying tumor growth [32,33]. At the same time, RFA can also enhance the immunity of patients by promoting the immune function of T cells, natural killer cells and macrophages, thereby limiting tumor cell proliferation [34]. However, clinical data indicated that RFA cannot significantly prolong the patients' five-year survival rate [6].…”

Section: Discussionmentioning

confidence: 99%

Possible involvement of HSP70 in pancreatic cancer cell proliferation after heat exposure and impact on RFA postoperative patient prognosis

Song

2019

Biochemistry and Biophysics Reports

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PurposeAs an alleviative treatment measured in patients with unresectable advanced pancreatic cancer, radiofrequency ablation (RFA) needed more clinical data to prove its advantages and to explore limitations in its utilization. This study was determined to observe the efficacy of RFA, and to explore its impact on perioperative periphery carcinoma as well as the normal pancreatic tissues.MethodsClinical data of 32 patients with pancreatic cancer accepted RFA surgery were collected. Followed up patients’ pain degree and the changes in serum tumor markers CA19-9 and CA 242 before and after surgery. Ex vivo, gave human pancreatic cancer cell line PANC-1 heat treatment to simulate the heat exposure condition periphery carcinoma was experienced during RFA surgery, and to observe the proliferation rate and HSP70 expression change compared with control group.ResultsOf the 32 patients, 1 died of upper gastrointestinal hemorrhage, and 29 survived for more than 5 months, 2 of which for more than 16 months. The average CA19-9 and CA 242 levels of the patients were significantly decreased in 3 months after surgery (t = 9.873, 5.978, P < 0.001). During in vitro experiments, the proliferation rate of PANC-1 cells after heating was significantly increased, accompanied with the increased HSP70 expression. The addition of HSP70 inhibitor can inhibit the rise of proliferation after heat therapy.ConclusionUtilizing RFA treat patients with unresectable advanced pancreatic cancer, could effectively relieve the pain, decline jaundice, and deduce tumor marker levels significantly. However, it failed to extend the long-term survival rate of the patients significantly. This study found that a higher proliferative rate accompanied with a higher HSP70 expression level were observed on in vitro cultured pancreatic carcinoma cells after heat treatment, which could be altered by HSP70 inhibitor. And these findings indicated that the heat exposure might impact periphery carcinoma during RFA surgery and HSP70 might play an important role in patients’ prognosis.

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Ultrasound-guided radiofrequency ablation enhances natural killer-mediated antitumor immunity against liver cancer

Cited by 10 publications

References 44 publications

Recent Advances in Molecular Mechanisms of the NKG2D Pathway in Hepatocellular Carcinoma

Recent Advances in Molecular Mechanisms of the NKG2D Pathway in Hepatocellular Carcinoma

Hypoxia-inducible gene 2 promotes the immune escape of hepatocellular carcinoma from nature killer cells through the interleukin-10-STAT3 signaling pathway

Possible involvement of HSP70 in pancreatic cancer cell proliferation after heat exposure and impact on RFA postoperative patient prognosis

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