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hepatocellular carcinoma immunotherapy

Kuan Hu, Zhi-Ming Wang, Juan-Ni Li, Sai Zhang, Zhong-Fu Xiao, Yi-Ming Tao
Spontaneous tumor hemorrhage (TH) is frequently observed in solid tumors including human hepatocellular carcinoma (HCC). TH implies fast-growing and worse tumor immunological microenvironment; however, the underlying mechanism remains largely unknown. CLEC1B is a signature gene highly associated with tumor progression. PD-L1 expression is a key biomarker predictive of immune checkpoint therapies, which showed astonishing effect on various types of tumor. We assume that, in HCC, TH may closely associate with the expression of these two molecules...
March 8, 2018: Translational Oncology
Jorge A Carrasquillo, Joseph A O'Donoghue, Volkan Beylergil, Shutian Ruan, Neeta Pandit-Taskar, Steven M Larson, Peter M Smith-Jones, Serge K Lyashchenko, Norihisa Ohishi, Toshihiko Ohtomo, Ghassan K Abou-Alfa
BACKGROUND: I-124 codrituzumab (aka GC33), an antibody directed at Glypican 3, was evaluated in patients with hepatocellular carcinoma (HCC). Fourteen patients with HCC underwent baseline imaging with I-124 codrituzumab (~ 185 MBq, 10 mg). Seven of these patients undergoing sorafenib/immunotherapy with 2.5 or 5 mg/kg of cold codrituzumab had repeat imaging, with co-infusion of I-124 codrituzumab, as part of their immunotherapy treatment. Three patients who progressed while on sorafenib/immunotherapy were re-imaged after a 4-week washout period to assess for the presence of antigen...
March 5, 2018: EJNMMI Research
Jean-Charles Nault, Peter R Galle, Jens U Marquardt
Hepatocellular carcinomas (HCC) are characterized by considerable phenotypic and molecular heterogeneity. Treatment and design of clinical trials are particularly challenging due a co-existing liver disease present in the majority of patients which limits aggressive therapeutic options. Despite positive results in recent phase III clinical trials, that confirmed the high value of antiangiogenic therapies for HCC in both first (sorafenib and lenvatinib) and second line (regorafenib and cabozantinib) treatment modalities, failure of several large randomized controlled clinical trials over the last 10 years underlines the necessity for innovative treatment strategies and implementation of findings from translational studies to overcome this unmet clinical need...
March 2, 2018: Journal of Hepatology
Guoming Hu, Shimin Wang
The prognostic role of tumor-infiltrating CD57-positive lymphocytes (CD57+ lymphocytes) in human solid tumors remains controversial. Herein, we conducted a meta-analysis including 26 published studies with 7656 patients identified from PubMed and EBSCO to assess the prognostic impact of tumor-infiltrating CD57+ lymphocytes in human solid tumors. We found that CD57+ lymphocyte infiltration significantly improved overall survival (OS) including 1 - year, 3 - year and 5 - year survival, and disease - free survival (DFS) in all types of solid tumors...
January 30, 2018: Oncotarget
Mahnaz Seifi-Alan, Roshanak Shamsi, Soudeh Ghafouri-Fard
Hepatocellular carcinoma (HCC) is a worldwide common malignancy with poor prognosis. Several studies have aimed at identification of appropriate biomarkers for early detection of this cancer. Cancer-testis antigens (CTAs) as a novel group of tumor-associated antigens have been demonstrated to be expressed in HCC samples as well as peripheral blood samples from these patients but not in the corresponding adjacent noncancerous samples. Such pattern of expression has provided them an opportunity to be used as immunotherapeutic targets...
April 2018: Immunotherapy
Wei Zhu, Yibing Peng, Lan Wang, Yuan Hong, Xiaotao Jiang, Qi Li, Heping Liu, Lei Huang, Juan Wu, Esteban Celis, Todd Merchen, Edward Kruse, Yukai He
Hepatocellular carcinoma (HCC) is the major form of liver cancer for which there is no effective therapy. Genetic modification with T cell receptors (TCR) specific for HCC-associated antigens, such as α-fetoprotein (AFP), can potentially redirect human T cells to specifically recognize and kill HCC tumor cells to achieve antitumor effects. In this study, by using lentivector and peptide immunization, we identified a population of CD8-T cells in HLA-A2 transgenic AAD mice that recognized AFP 158 epitope on human HCC cells...
February 14, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Shengbin Shi, Quan Rao, Chuangnian Zhang, Xiuyuan Zhang, Yibo Qin, Zuoxing Niu
Advanced hepatocellular carcinoma (HCC) has limited therapeutic options. Immunotherapy is a promising treatment, while sorafenib is a first-line drug-based treatment for advanced HCC. However, the efficacy of sorafenib and immunotherapy in combination, have not been clearly evaluated. Sorafenib treatment has been shown to promote immunosuppression by increasing hypoxia in orthotopic HCC models. Here, we found that sorafenib treatment in mice with orthotopic HCC increased the expression of inhibitor programmed death-ligand 1 (PD-L1) and T-regulatory cells in tumor tissues...
January 27, 2018: Translational Oncology
Wang Yanru, Bai Zhenyu, Niu Zhengchuan, Qi Qi, Liang Chunmin, Yao Weiqiang
Chemokines are essential coordinators of cellular migration and cell-cell interactions, therefore considerable attention has been paid to the application of chemokines to cancer immunotherapy. In this study, we screened for the expression levels of 58 human chemokines/chemokine receptors in hepatocellular carcinoma (HCC) by using samples from the TCGA LIHC cohort and found 16 consistently down-regulated and 11 up-regulated chemokine genes in HCC compared with normal samples. Furthermore, the expressions of XCR1 were verified by Western blot in liver cancer cell lines...
February 2, 2018: Biochemical and Biophysical Research Communications
Masashi Kumagai, Eishiro Mizukoshi, Toshikatsu Tamai, Masaaki Kitahara, Tatsuya Yamashita, Kuniaki Arai, Takeshi Terashima, Noriho Iida, Kazumi Fushimi, Shuichi Kaneko
BACKGROUND AND AIMS: Human telomerase reverse transcriptase (hTERT) is a catalytic enzyme involved in telomere elongation. It is expressed in many tumors, including hepatocellular carcinoma (HCC). The purpose of the present study was to identify major histocompatibility complex (MHC) class II-restricted helper T cell epitopes derived from hTERT in patients with HCC. METHODS: TEPITOPE software was used to predict helper T cell epitopes based on the entire amino acid sequence of hTERT, and peptides were synthesized based on the predicted sequence...
February 6, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
Shunli Shen, Hong Peng, Ye Wang, Ming Xu, Manxia Lin, Xiaoyan Xie, Baogang Peng, Ming Kuang
BACKGROUND: Radiofrequency ablation (RFA) can not only effectively kill hepatocellular carcinoma (HCC) tumour cells but also release tumour antigens that can provoke an immune response. However, there is no consensus regarding which antigens could constitutively be generated after RFA and could potentiate the immune response. The aim of this study was to identify these immune-potentiating antigens. METHODS: We performed two-dimensional electrophoresis (2-DE) and MALDI-TOF-MS/MS analyses on serum obtained before and after RFA from 5 HCC patients...
January 31, 2018: BMC Cancer
Marc Ringelhan, Dominik Pfister, Tracy O'Connor, Eli Pikarsky, Mathias Heikenwalder
In contrast to most other malignancies, hepatocellular carcinoma (HCC), which accounts for approximately 90% of primary liver cancers, arises almost exclusively in the setting of chronic inflammation. Irrespective of etiology, a typical sequence of chronic necroinflammation, compensatory liver regeneration, induction of liver fibrosis and subsequent cirrhosis often precedes hepatocarcinogenesis. The liver is a central immunomodulator that ensures organ and systemic protection while maintaining immunotolerance...
March 2018: Nature Immunology
Yonghong Zhang, Sophie Petropoulos, Jinhua Liu, David Cheishvili, Rudy Zhou, Sergiy Dymov, Kang Li, Ning Li, Moshe Szyf
Background: The idea that changes to the host immune system are critical for cancer progression was proposed a century ago and recently regained experimental support. Results: Herein, the hypothesis that hepatocellular carcinoma (HCC) leaves a molecular signature in the host peripheral immune system was tested by profiling DNA methylation in peripheral blood mononuclear cells (PBMC) and T cells from a discovery cohort (n = 69) of healthy controls, chronic hepatitis, and HCC using Illumina 450K platform and was validated in two validation sets (n = 80 and n = 48) using pyrosequencing...
2018: Clinical Epigenetics
Ravi Salgia, Prakash Kulkarni, Prakash S Gill
The erythropoietin-producing hepatocellular carcinoma (Eph) receptors are the largest family of receptor tyrosine kinases (RTKs) that include two major subclasses, EphA and EphB. They form an important cell communication system with critical and diverse roles in a variety of biological processes during embryonic development. However, dysregulation of the Eph/ephrin interactions is implicated in cancer contributing to tumour growth, metastasis, and angiogenesis. Here, we focus on EphB4 and review recent developments in elucidating its role in upper aerodigestive malignancies to include lung cancer, head and neck cancer, and mesothelioma...
January 21, 2018: Biochimica et Biophysica Acta
Myth T S Mok, Jingying Zhou, Wenshu Tang, Xuezhen Zeng, Antony W Oliver, Simon E Ward, Alfred S L Cheng
Cyclin-dependent kinase 20 (CDK20), or more commonly referred to as cell cycle-related kinase (CCRK), is the latest member of CDK family with strong linkage to human cancers. Accumulating studies have reported the consistent overexpression of CCRK in cancers arising from brain, colon, liver, lung and ovary. Such aberrant up-regulation of CCRK is clinically significant as it correlates with tumor staging, shorter patient survival and poor prognosis. Intriguingly, the signalling molecules perturbed by CCRK are divergent and cancer-specific, including the cell cycle regulators CDK2, cyclin D1, cyclin E and RB in glioblastoma, ovarian carcinoma and colorectal cancer, and KEAP1-NRF2 cytoprotective pathway in lung cancer...
January 21, 2018: Pharmacology & Therapeutics
Guillermo D Mazzolini, Mariana Malvicini
Hepatocellular carcinoma (HCC) is the second cause of cancer-related death in the world and is the main cause of death in cirrhotic patients. Unfortunately, the incidence of HCC has grown significantly in the last decade. Curative treatments such as surgery, liver transplantation or percutaneous ablation can only be applied in less than 30% of cases. The multikinase inhibitor sorafenib is the first line therapy for advanced HCC. Regorafenib is the standard of care for second-line patients. However, novel and more specific potent therapeutic approaches for advanced HCC are still needed...
2018: Medicina
Ying Wang, Xijing Yang, Yi Yu, Zenghui Xu, Yan Sun, Hui Liu, Jingbo Cheng, Min Liu, Bibo Sha, Linfang Li, Na Ding, Zhong Li, Huajun Jin, Qijun Qian
Purpose The aim of this study was to evaluate the clinical response of immunotherapy with dendritic cell-cytotoxic T lymphocytes (DC-CTLs) in patients with hepatocellular carcinoma (HCC). Method Sixty-eight patients with a confirmed diagnosis of HCC and who received follow-up until December 2015 were enrolled. We measured immune phenotypes of DCs and activated T cells using flow cytometry and clinical indexes using an electrochemiluminescence method. Results DCs exhibited up-regulation of the maturation markers CD83, CD80, CD11c, and CD86 on day8...
2018: Journal of Cancer
Junyong Zhang, Nian Wu, Zhengrong Lian, Huyi Feng, Qing Jiang, Xianfeng Chen, Jianping Gong, Zhengrong Qiao
The combination of radiotherapy and immunotherapy has shown great promise in eradicating tumors. For example, 125I radioactive particle implantation and cytokine-induced killer cell therapies have demonstrated efficacy in treating hepatocellular carcinoma. However, the mechanism of this combination therapy remains unknown. In this study, we utilized cytokine-induced killer cells obtained from human peripheral blood mononuclear cells along with 125I radioactive particle implantation to treat subcutaneous hepatocellular carcinoma xenograft tumors in BALB/c nude mice...
December 2017: Technology in Cancer Research & Treatment
Kai Dai, Yabing Huang, Zubing Chen, Xiaomei Sun, Lihua Yang, Yingan Jiang
Natural killer cell (NK cell)-based immunotherapy is a promising therapeutic strategy for hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying the regulation of NK cell function in the tumor sites are not completely elucidated. In this study, we identified the enhanced expression of kelch repeat and BTB (POZ) domain containing 2 (Kbtbd2) in intratumoral NK cells in a mouse HCC implantation model as a negative regulator of NK cells. To investigate this interaction,, we used a Tet-on inducible expression system to control Kbtbd2 expression in an immortalized mouse NK cell line KIL C...
January 13, 2018: European Journal of Immunology
Jing-Hua Pan, Hong Zhou, Xiao-Xu Zhao, Hui Ding, Wei Li, Li Qin, Yun-Long Pan
Communication between hepatocellular carcinoma (HCC) cells and their environment is essential for the development and progression of HCC. Exosomes, which are microvesicles secreted by a number of cell types, are carriers of intercellular information and regulate the tumour microenvironment. Studies have demonstrated that exosomes are involved in the communication between HCC cells, endothelial cells and stem cells, and that they serve important roles in the metastasis and invasion, immune evasion and immunotherapy of HCC...
January 11, 2018: International Journal of Molecular Medicine
Caryn L Elsegood, Janina Ee Tirnitz-Parker, John K Olynyk, George Ct Yeoh
The global prevalence of liver cancer is rapidly rising, mostly as a result of the amplified incidence rates of viral hepatitis, alcohol abuse and obesity in recent decades. Treatment options for liver cancer are remarkably limited with sorafenib being the gold standard for advanced, unresectable hepatocellular carcinoma but offering extremely limited improvement of survival time. The immune system is now recognised as a key regulator of cancer development through its ability to protect against infection and chronic inflammation, which promote cancer development, and eliminate tumour cells when present...
November 2017: Clinical & Translational Immunology
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