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hepatocellular carcinoma immunotherapy

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https://www.readbyqxmd.com/read/29150490/gut-roundtable-meeting-paper-selected-recent-advances-in-hepatocellular-carcinoma
#1
REVIEW
Alexander Gerbes, Fabien Zoulim, Herbert Tilg, Jean-François Dufour, Jordi Bruix, Valérie Paradis, Riad Salem, Markus Peck-Radosavljevic, Peter R Galle, Tim F Greten, Jean-Charles Nault, Matias A Avila
Hepatocellular carcinoma (HCC) ranks number three among the most frequent causes of death from solid tumors worldwide. With obesity and fatty liver diseases as risk factors on the rise, HCC represents an ever increasing challenge. While there is still no curative treatment for most patients numerous novel drugs have been proposed, but most ultimately failed in phase III trials. This manuscript targets therapeutic advances and most burning issues. Expert key point summaries and urgent research agenda are provided regarding risk factors, including microbiota, need for prognostic and predictive biomarkers and the equivocal role of liver biopsy...
November 17, 2017: Gut
https://www.readbyqxmd.com/read/29150141/hepatocellular-carcinoma-in-the-era-of-immunotherapy
#2
REVIEW
Hao-Wen Sim, Jennifer Knox
Hepatocellular carcinoma is a common malignancy which usually emerges on a background of chronic liver disease. Unfortunately, with contemporary management, patients with advanced hepatocellular carcinoma have few treatment options, and prognosis is poor. The emergence of immunotherapy has afforded new therapeutic opportunities. This article reviews the clinical evidence for immunotherapy in advanced hepatocellular carcinoma and presents ideas for future drug development.
November 14, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/29145036/liver-immunotolerance-and-hepatocellular-carcinoma-patho-physiological-mechanisms-and-therapeutic-perspectives
#3
REVIEW
Gaël S Roth, Thomas Decaens
At the moment of the diagnosis of hepatocellular carcinoma (HCC), 70% of patients have only access to palliative treatments, with very few therapeutic options. Liver immunology is very specific, and liver immunotolerance is particularly developed because of the constant and massive influx of antigens. Deregulation of hepatic immunotolerance is implicated in chronic liver diseases development and particularly in liver carcinogenesis. For these reasons, HCC may be an excellent candidate for anticancer immunotherapies such as immune checkpoint inhibitors targeting CTLA-4 and PD-L1/PD-1...
November 13, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29138342/immunotherapy-of-hepatocellular-carcinoma-facts-and-hopes
#4
Mercedes Iñarrairaegui, Ignacio Melero, Bruno Sangro
Treatment of patients with hepatocellular carcinoma in the advanced stage remains a great challenge, with very few drugs approved. After decades of failures of immune therapies, immune checkpoint inhibitors have emerged as potentially effective treatments for patients with hepatocellular carcinoma in the advanced stage. Immune checkpoints, including human cancer, cytotoxic T-lymphocyte protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1), are surface proteins expressed in a variety of immune cells, and mostly provide immunosuppressive signals...
November 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29132013/chimeric-antigen-receptor-modified-t-cells-redirected-to-epha2-for-the-immunotherapy-of-non-small-cell-lung-cancer
#5
Ning Li, Shaohui Liu, Mingjiao Sun, Wei Chen, Xiaogang Xu, Zhu Zeng, Yemin Tang, Yongquan Dong, Alex H Chang, Qiong Zhao
Erythropoietin-producing hepatocellular carcinoma A2 (EphA2) is overexpressed in more than 90% of non-small cell lung cancer (NSCLC) but not significantly in normal lung tissue. It is therefore an important tumor antigen target for chimeric antigen receptors (CAR)-T-based therapy in NSCLC. Here, we developed a specific CAR targeted to EphA2, and the anti-tumor effects of this CAR were investigated. A second generation CAR with co-stimulatory receptor 4-1BB targeted to EphA2 was developed. The functionality of EphA2-specific T cells in vitro was tested with flow cytometry and real-time cell electronic sensing system assays...
November 10, 2017: Translational Oncology
https://www.readbyqxmd.com/read/29119057/dendritic-cells-based-immunotherapy
#6
REVIEW
Na Shang, Matteo Figini, Junjie Shangguan, Bin Wang, Chong Sun, Liang Pan, Quanhong Ma, Zhuoli Zhang
Dendritic cells (DCs) are the most potent antigen-presenting cells, and tumor antigen-loaded DCs (DC-vaccines) can activate tumor-specific cytotoxic T lymphocytes (CTLs) in lymphatic tissues. DC vaccination is a newly emerging and potent form of cancer immunotherapy and has clinically relevant mechanisms of action with great potential for the systemic treatment of cancers. However, clinical trials have demonstrated relatively poor therapeutic efficacy. The efficacy of DC-vaccines is strongly influenced by various techniques for the priming antigen loading onto DCs and their ability to migrate to the draining lymph nodes (LNs)...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29115604/genetically-engineered-recombinant-adenovirus-expressing-interleukin%C3%A2-2-for-hepatocellular-carcinoma-therapy
#7
Yunpeng Sun, Huanhuan Wu, Gang Chen, Xiaming Huang, Yunfeng Shan, Hongqi Shi, Qiyu Zhang, Yihu Zheng
Regulatory and effector T cells possess immunological cytotoxicity for tumor cells in the tumor microenvironment during tumor progression and are the primary suppressors inhuman cancer therapy. Interleukin‑2 (IL‑2) is an anticancer cytokine, which triggers human innate and adaptive immunity by stimulating T cell propagation and lymphocyte infiltration into tumor sites. IL‑2 has been used successfully for cancer therapy. Recombinant adenovirus expressing IL‑2 (rAd‑IL‑2) injection is a gene therapy agent that may improve prognosis of hepatocellular carcinoma (HCC) patients...
October 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29113661/program-death-1-immune-checkpoint-and-tumor-microenvironment-in-malignant-liver-tumors
#8
REVIEW
Demetrios Moris, Amir A Rahnemai-Azar, XuFeng Zhang, Ioannis Ntanasis-Stathopoulos, Diamantis I Tsilimigras, Jeffery Chakedis, Chrysoula Argyrou, John J Fung, Timothy M Pawlik
Hepatic malignancies are one of the leading causes of cancer death globally. Considering the limited efficacy of current standard treatments in management of patients with advanced liver cancers, there has been a growing interest in identifying novel therapies. Despite achieving promising results in initial clinical trials, the therapeutic benefit of immunotherapy is limited due to strong immune-tolerogenic characteristics of liver tumors. Therapeutic regimens that impede tumor immunosuppressive mechanisms or elaborate tumor-specific immunity may improve clinical outcomes of patients with liver malignancies...
December 2017: Surgical Oncology
https://www.readbyqxmd.com/read/29109772/the-anti-tumor-effects-of-m1-macrophage-loaded-poly-ethylene-glycol-and-gelatin-based-hydrogels-on-hepatocellular-carcinoma
#9
Alberto Daniel Guerra, Oscar W H Yeung, Xiang Qi, W John Kao, Kwan Man
Background and Aims: Recently we reported that direct injection of M1 macrophages significantly caused tumor regression in vivo. Despite the promising result, a major limitation in translating this approach is the induction of acute inflammatory response. To improve the strategy, a biocompatible scaffold for cell presentation and support is essential to control cell fate. Here, we aimed to elucidate the anti-tumor effects of a poly(ethylene glycol) diacrylate (PEGdA) and thiolated gelatin poly(ethylene glycol) (Gel-PEG-Cys) cross-linked hydrogels capsulated with M1 macrophages in both in vitro and in vivo disease models...
2017: Theranostics
https://www.readbyqxmd.com/read/29093082/according-to-hcv-infection-stage-il-7-plus-4-1bb-triggering-alone-or-combined-with-pd-1-blockade-increases-traf1-low-hcv-specific-cd8-cell-reactivity
#10
Elia Moreno-Cubero, Dolores Subirá, Eduardo Sanz-de-Villalobos, Trinidad Parra-Cid, Antonio Madejón, Joaquín Miquel, Antonio Olveira, Alejandro González-Praetorius, Javier García-Samaniego, Juan-Ramón Larrubia
Hepatitis C virus (HCV)-specific CD8(+) T cells suffer a progressive exhaustion during persistent HCV infection (PI). This process could involve the positive immune checkpoint 4-1BB/4-1BBL, through the loss of its signal transducer TRAF1. To address this issue, peripheral HCV-specific CD8(+) T cells (Pentamer(+)/CD8(+)) from patients with PI and resolved infection after treatment (RI) were studied. Duration of HCV infection and liver fibrosis progression rate inversely correlated with the likelihood of detecting peripheral pentamer(+)/CD8(+) cells...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29090321/cross-talk-between-tnf-%C3%AE-and-ifn-%C3%AE-signaling-in-induction-of-b7-h1-expression-in-hepatocellular-carcinoma-cells
#11
Na Li, Jianing Wang, Na Zhang, Mengwei Zhuang, Zhaoyun Zong, Jiahuan Zou, Guosheng Li, Xiaoyan Wang, Huaiyu Zhou, Lining Zhang, Yongyu Shi
Clinical benefit from immunotherapy of B7-H1/PD-1 checkpoint blockade indicates that it is important to understand the regulatory mechanism of B7-H1 expression in cancer cells. As an adaptive response to the endogenous antitumor immunity, B7-H1 expression is up-regulated in HCC cells. B7-H1 expression is induced mainly by IFN-γ released from tumor-infiltrating T cells in HCC. In addition, HCC is a prototype of inflammation-related cancer and TNF-α is a critical component of inflammatory microenvironment of HCC...
October 31, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29052780/immunotherapy-for-hepatocellular-carcinoma-patients-is-it-ready-for-prime-time
#12
REVIEW
Joseph M Obeid, Paul R Kunk, Victor M Zaydfudim, Timothy N Bullock, Craig L Slingluff, Osama E Rahma
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the second most common cause of cancer death worldwide. Current treatment options for patients with intermediate and advanced HCC are limited, and there is an unmet need for novel therapeutic approaches. HCC is an attractive target for immunomodulation therapy, since it arises in an inflammatory milieu due to hepatitis B and C infections and cirrhosis. However, a major barrier to the development and success of immunotherapy in patients with HCC is the liver's inherent immunosuppressive function...
October 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29051790/current-immunotherapeutic-strategies-in-hepatocellular-carcinoma-recent-advances-and-future-directions
#13
REVIEW
Hwi Young Kim, Joong-Won Park
Hepatocellular carcinoma (HCC) is a common and serious health problem with high mortality. Treatment for HCC remains largely unsatisfactory owing to its high recurrence rates and frequent accompanying cirrhosis. In addition, the unique immune environment of the liver promotes tolerance, which, in conjunction with immune evasion by the disease, makes HCC a less promising target for conventional immunotherapy. However, recent advances in the immunotherapy have led to novel approaches to overcome these obstacles by manipulating and enhancing tumor-specific immune responses against HCC by using various modalities, such as cancer vaccines and immune checkpoint blockade...
October 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/28987386/autophagy-in-the-inflammation-carcinogenesis-pathway-of-liver-and-hcc-immunotherapy
#14
Sizhe Yu, Yu Wang, Li Jing, F X Claret, Qing Li, Tao Tian, Xuan Liang, Zhiping Ruan, Lili Jiang, Yu Yao, Kejun Nan, Yi Lv, Hui Guo
Autophagy plays a dual role in many types of cancer, such as hepatocellular carcinoma (HCC). Autophagy seems to be inhibited and functions as a tumor-suppression mechanism in the "inflammation-carcinogenesis" pathway of the liver, including hepatitis B virus and hepatitis C virus, alcoholic steatohepatitis and non-alcoholic steatohepatitis related HCC. However, in established tumors, autophagy plays a tumor-promoting role. Because of the varied function of autophagy in HCC, we hypothesized p62 as a marker to evaluate the autophagic level...
October 5, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28971150/lambda-phage-based-vaccine-induces-antitumor-immunity-in-hepatocellular-carcinoma
#15
Yoshifumi Iwagami, Sarah Casulli, Katsuya Nagaoka, Miran Kim, Rolf I Carlson, Kosuke Ogawa, Michael S Lebowitz, Steve Fuller, Biswajit Biswas, Solomon Stewart, Xiaoqun Dong, Hossein Ghanbari, Jack R Wands
BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a difficult to treat tumor with a poor prognosis. Aspartate β-hydroxylase (ASPH) is a highly conserved enzyme overexpressed on the cell surface of both murine and human HCC cells. METHODS: We evaluated therapeutic effects of nanoparticle lambda (λ) phage vaccine constructs against ASPH expressing murine liver tumors. Mice were immunized before and after subcutaneous implantation of a syngeneic BNL HCC cell line...
September 2017: Heliyon
https://www.readbyqxmd.com/read/28939663/hepatoma-intrinsic-ccrk-inhibition-diminishes-myeloid-derived-suppressor-cell-immunosuppression-and-enhances-immune-checkpoint-blockade-efficacy
#16
Jingying Zhou, Man Liu, Hanyong Sun, Yu Feng, Liangliang Xu, Anthony W H Chan, Joanna H Tong, John Wong, Charing Ching Ning Chong, Paul B S Lai, Hector Kwong-Sang Wang, Shun-Wa Tsang, Tyler Goodwin, Rihe Liu, Leaf Huang, Zhiwei Chen, Joseph Jy Sung, King Lau Chow, Ka Fai To, Alfred Sze-Lok Cheng
OBJECTIVE: Myeloid-derived suppressor cells (MDSCs) contribute to tumour immunosuppressive microenvironment and immune-checkpoint blockade resistance. Emerging evidence highlights the pivotal functions of cyclin-dependent kinases (CDKs) in tumour immunity. Here we elucidated the role of tumour-intrinsic CDK20, or cell cycle-related kinase (CCRK) on immunosuppression in hepatocellular carcinoma (HCC). DESIGN: Immunosuppression of MDSCs derived from patients with HCC and relationship with CCRK were determined by flow cytometry, expression analyses and co-culture systems...
September 22, 2017: Gut
https://www.readbyqxmd.com/read/28928158/characterization-of-the-immune-microenvironment-in-hepatocellular-carcinoma-hcc
#17
Mark Yarchoan, Dongmei Xing, Lan Luan, Haiying Xu, Rajni Sharma, Aleksandra Popovic, Timothy M Pawlik, Amy K Kim, Qingfeng Zhu, Elizabeth M Jaffee, Janis Taube, Robert A Anders
PURPOSE: Hepatocellular carcinoma (HCC) often arises in the setting of chronic liver inflammation and may be responsive to novel immunotherapies. EXPERIMENTAL DESIGN: To characterize the immune microenvironment in HCC, immunohistochemical (IHC) staining was performed for CD8 positive T lymphocytes, PD-1 positive and LAG-3 positive lymphocytes, CD163 positive macrophages, and PD-L1 expression in tumor and liver background from 29 cases of resected HCC. RESULTS: Expression of CD8 was reduced in tumor and expression of CD163 was reduced at the tumor interface...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28893090/an-in-depth-review-of-chemical-angiogenesis-inhibitors-for-treating-hepatocellular-carcinoma
#18
Jean-Luc Raoul, Marine Gilabert, Xavier Adhoute, Julien Edeline
Hepatocellular carcinoma (HCC) is a frequent and severe complication of cirrhosis. Most HCC patients initially present with or progress to advanced stage disease and require systemic treatment. As hypervascularization is a major characteristic of HCC, antiangiogenic drugs have been tested. Areas covered: In this review, we summarize data on the use of drugs targeting the angiogenesis. Despite many trials, in 2017 only 3 drugs, all antiangiogenic, have demonstrated efficacy in first (sorafenib, lenvatinib) or second line (regorafenib) treatment of advanced HCC...
October 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28867968/advances-and-future-directions-in-the-treatment-of-hepatocellular-carcinoma
#19
Ashil J Gosalia, Paul Martin, Patricia D Jones
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Liver transplant is considered the gold standard for curative therapy for HCC when patients are not candidates for surgical resection or ablation. Because a subset of patients with HCC have a survival rate with liver transplantation that is comparable to that of cirrhotic patients without tumors, the organ allocation system allows for increased priority for transplant in potential recipients within the Milan criteria...
July 2017: Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28863950/the-state-of-t-cells-before-cryopreservation-effects-on-post-thaw-proliferation-and-function
#20
Ying Luo, Peng Wang, Hui Liu, Zhengyan Zhu, Chenglong Li, Yingtang Gao
AIM: We aim to assess the effect of the state of T cells before cryopreservation on the post-thaw proliferative capacity, phenotype and functional response. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from a hepatocellular carcinoma (HCC) patient, and the T cells were frozen during cell culture according to our experimental design. After a period of re-culture, the proliferative capacity of the cryopreserved cells, the expression of T cell surface markers and the secretion of IFN-γ and IL-10 were assayed...
August 31, 2017: Cryobiology
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