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hepatocellular carcinoma immunotherapy

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https://www.readbyqxmd.com/read/28939663/hepatoma-intrinsic-ccrk-inhibition-diminishes-myeloid-derived-suppressor-cell-immunosuppression-and-enhances-immune-checkpoint-blockade-efficacy
#1
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
#2
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
#3
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
#4
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
#5
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 29, 2017: Cryobiology
https://www.readbyqxmd.com/read/28856237/t-cell-activating-mesenchymal-stem-cells-as-a-biotherapeutic-for-hcc
#6
Arpad Szoor, Abishek Vaidya, Mireya Paulina Velasquez, Zhuyong Mei, Daniel L Galvan, David Torres, Adrian Gee, Andras Heczey, Stephen Gottschalk
The outcome for advanced stage hepatocellular carcinoma (HCC) remains poor, highlighting the need for novel therapies. Genetically modified mesenchymal stem cells (MSCs) are actively being explored as cancer therapeutics due to their inherent ability to migrate to tumor sites. We reasoned that MSCs can be genetically modified to redirect T cells to Glypican-3 (GPC3)(+) HCC, and genetically modified these with viral vectors encoding a GPC3/CD3 bispecific T cell engager (GPC3-ENG), a bispecifc T cell engager specific for an irrelevant antigen (EGFRvIII), and/or costimulatory molecules (CD80 and 41BBL)...
September 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28854942/the-biology-of-hepatocellular-carcinoma-implications-for-genomic-and-immune-therapies
#7
REVIEW
Galina Khemlina, Sadakatsu Ikeda, Razelle Kurzrock
Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is a leading cause of cancer-related death worldwide. It is highly refractory to most systemic therapies. Recently, significant progress has been made in uncovering genomic alterations in HCC, including potentially targetable aberrations. The most common molecular anomalies in this malignancy are mutations in the TERT promoter, TP53, CTNNB1, AXIN1, ARID1A, CDKN2A and CCND1 genes. PTEN loss at the protein level is also frequent. Genomic portfolios stratify by risk factors as follows: (i) CTNNB1 with alcoholic cirrhosis; and (ii) TP53 with hepatitis B virus-induced cirrhosis...
August 30, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28847032/learning-the-roles-of-the-hepatic-adaptive-immune-system-in-hepatocellular-carcinoma-nature-s-guide-for-successful-cancer-immunotherapy
#8
Mathias Heikenwälder, Eli Pikarsky
No abstract text is available yet for this article.
August 2017: Seminars in Liver Disease
https://www.readbyqxmd.com/read/28836129/enlighting-the-shadow-for-advanced-hepatocellular-carcinoma-immunotherapy-with-immune-checkpoint-inhibitors
#9
REVIEW
Berksoy Sahin
Hepatocellular carcinoma has still been one of the cancer with increasing incidence and highest mortality rate in the world. Although many new promising developments have been defined in hepatocarcinogenesis, with a short survival the treatment of patients with advanced hepatocellular carcinoma is an emerging issue. On the recent decade, only one anti-angiogenic agent sorafenib improved overall survival with costing a hardly manageable toxicity. Novel immunotherapeutic agents, especially immune checkpoint inhibitors are on the edge of more effective but less toxic treatments for these patients...
August 23, 2017: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/28827021/toward-cure-chronic-hepatitis-b-infection-and-hepatocellular-carcinoma-prevention-lessons-learned-from-nucleos-t-ide-analogues-therapy
#10
REVIEW
Soheil Tavakolpour, Hajar Sadat Mirsafaei, Somayeh Elkaei Behjati, Mojtaba Ghasemiadl, Meisam Akhlaghdoust, Shahnaz Sali
Nucleos(t)ide analogues (NAs) could successfully suppress hepatitis B virus (HBV) replication in patients with chronic hepatitis B (CHB). However, due to probable development of drug resistance or low/delayed response, these treatments may not be satisfactory. In addition to the HBV DNA polymerase inhibiting activity, these drugs could lead to changes in cytokines profiles. It is important to monitor these changes so that they could be used as target of treatment. Evaluating the previously reported immune responses due to NAs treatments, it was concluded that interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin-4 (IL-4), and IL-12 increase after the treatment...
August 5, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28811965/adjuvant-immunotherapy-with-autologous-dendritic-cells-for-hepatocellular-carcinoma-randomized-phase-ii-study
#11
Jeong-Hoon Lee, Won Young Tak, Yoon Lee, Min-Kyu Heo, Jae-Sung Song, Hak-Yeop Kim, Soo Young Park, Si Hyun Bae, Joon Hyeok Lee, Jeong Heo, Ki-Hwan Kim, Yong-Soo Bae, Yoon Jun Kim
Our previous phase I/IIA study showed that autologous dendritic cells (DCs) pulsed with tumor-associated antigens are well tolerated in patients with hepatocellular carcinoma (HCC). In this randomized, multicenter, open-label, phase II trial, we investigated the efficacy and safety of this DC-based adjuvant immunotherapy with 156 patients, who treated for HCC with no evidence of residual tumor after standard treatment modalities. Patients were randomly assigned to immunotherapy (n = 77; injection of 3 × 10(7) DC cells, six times over 14 weeks) or control (n = 79; no treatment)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28780700/natural-killer-cells-in-hepatocellular-carcinoma-current-status-and-perspectives-for-future-immunotherapeutic-approaches
#12
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/28758114/immunotherapy-in-gastrointestinal-cancers
#13
REVIEW
Letizia Procaccio, Marta Schirripa, Matteo Fassan, Loredana Vecchione, Francesca Bergamo, Alessandra Anna Prete, Rossana Intini, Chiara Manai, Vincenzo Dadduzio, Alice Boscolo, Vittorina Zagonel, Sara Lonardi
Gastrointestinal cancers represent a major public health problem worldwide. Immunotherapeutic strategies are currently under investigation in this setting and preliminary results of ongoing trials adopting checkpoint inhibitors are striking. Indeed, although a poor immunogenicity for GI has been reported, a strong biological rationale supports the development of immunotherapy in this field. The clinical and translational research on immunotherapy for the treatment of GI cancers started firstly with the identification of immune-related mechanisms possibly relevant to GI tumours and secondly with the development of immunotherapy-based agents in clinical trials...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28754304/a-natural-ccr2-antagonist-relieves-tumor-associated-macrophage-mediated-immunosuppression-to-produce-a-therapeutic-effect-for-liver-cancer
#14
Wenbo Yao, Qian Ba, Xiaoguang Li, Huiliang Li, Shoude Zhang, Ya Yuan, Feng Wang, Xiaohua Duan, Jingquan Li, Weidong Zhang, Hui Wang
Hepatocellular carcinoma (HCC) is a common malignant tumor in the digestive tract with limited therapeutic choices. Although sorafenib, an orally administered multikinase inhibitor, has produced survival benefits for patients with advanced HCC, favorable clinical outcomes are limited due to individual differences and resistance. The application of immunotherapy, a promising approach for HCC is urgently needed. Macrophage infiltration, mediated by the CCL2/CCR2 axis, is a potential immunotherapeutic target. Here, we report that a natural product from Abies georgei, named 747 and related in structure to kaempferol, exhibits sensitivity and selectivity as a CCR2 antagonist...
August 2017: EBioMedicine
https://www.readbyqxmd.com/read/28732118/pd-1-checkpoint-blockade-in-combination-with-an-mtor-inhibitor-restrains-hepatocellular-carcinoma-growth-induced-by-hepatoma-cell-intrinsic-pd-1
#15
Hui Li, Xiaoqiang Li, Shuang Liu, Lei Guo, Bo Zhang, Jubo Zhang, Qinghai Ye
Inhibitors of PD-1 administered as single agents have resulted in durable tumor regression in advanced cancer patients. However, only a minority of cancer patients respond to anti PD-1 immunotherapy. Here, we show that PD-1 expression in hepatocellular carcinoma (HCC) promotes tumor growth independently of adaptive immunity. Knockdown of PD-1 suppress tumor growth, whereas PD-1 overexpression enhances tumorigenesis in immunodeficient xenografted mice. Mechanistically, PD-1 binds the downstream mTOR effectors eukaryotic initiation factor 4E (eIF4E) and ribosomal protein S6 (S6), thus promoting their phosphorylation...
July 21, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28706578/systemic-treatment-of-hepatocellular-carcinoma-past-present-and-future
#16
REVIEW
Esther Una Cidon
Hepatocellular carcinoma (HCC) is a common neoplasia which represents the second leading cause of cancer related death. Most cases occur in developing countries, but its incidence is rising in Western countries due to hepatitis C. Although hepatitis therapies have evolved and the HCC screening has increased in several areas, 40% present with advanced disease which is only amenable for palliative systemic treatment. HCC continues posing a challenge, in part due to the inherent chemoresistance of this neoplasia, the pharmacologic challenges due to an ill liver, difficulty in assessing radiological responses accurately, etc...
June 28, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28693071/-effect-of-transcatheter-arterial-chemoembolization-combined-with-thymosin-alpha-1-on-the-autophagy-of-immune-cells-from-advanced-hepatocellular-carcinoma
#17
S J Fang, L Y Zheng, Z W Zhao, X X Fan, M Xu, J S Ji
Objective: To investigate the effect of transcatheter arterial chemoembolization(TACE)combined with thymosin alpha1(Tα1)on the autophagy of immune cells from advanced hepatocellular carcinoma. Methods: A total of 30 patients with advanced liver cancer enrolled in Lishui Central Hospital from September 2015 to June 2016 were collected in this study. The average age of patients was 16-75(56±12) years. All patients were treated with TACE after enrolled in hospital in a week. Patients were divided into TACE group and TACE+ Tα1 treatment group(15 cases in each group)...
July 4, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28674001/delineation-of-an-immunosuppressive-gradient-in-hepatocellular-carcinoma-using-high-dimensional-proteomic-and-transcriptomic-analyses
#18
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/28643325/surface-expression-of-anti-cd3scfv-stimulates-locoregional-immunotherapy-against-hepatocellular-carcinoma-depending-on-the-e1a-engineered-human-umbilical-cord-mesenchymal-stem-cells
#19
Qing Zhang, Xiang-Fei Yuan, Yang Lu, Zhen-Zhen Li, Shi-Qi Bao, Xiao-Long Zhang, Yuan-Yuan Yang, Dong-Mei Fan, Yi-Zhi Zhang, Chen-Xuan Wu, Hong-Xing Guo, Yan-Jun Zhang, Zhou Ye, Dong-Sheng Xiong
Tumor antigens is at the core of cancer immunotherapy, however, the ideal antigen selection is difficult especially in poorly immunogenic tumors. In this study, we designed a strategy to modify hepatocellular carcinoma (HCC) cells by surface expressing anti-CD3scfv within the tumor site strictly, which depended on the E1A-engineered human umbilical cord mesenchymal stem cells (HUMSC.E1A) delivery system. Subsequently, membrane-bound anti-CD3scfv actived the lymphocytes which lysed HCC cells bypassing the expression of antigens or MHC restriction...
October 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28638219/spontaneous-regression-of-hepatocellular-carcinoma-a-mini-review
#20
REVIEW
Akira Sakamaki, Kenya Kamimura, Satoshi Abe, Atsunori Tsuchiya, Masaaki Takamura, Hirokazu Kawai, Satoshi Yamagiwa, Shuji Terai
Spontaneous tumor regression is an extremely rare phenomenon in the oncology field. However, there are several case reports resulted in the regression of hepatocellular carcinoma (HCC) and the accumulation of clinical information and analyses of the mechanism can contribute to the development of a novel therapy. For this purpose, we have carefully reviewed 23 cases of spontaneously regressed HCC published in recent 5 years and our case. The information regarding the tumor size, tumor marker, treatments, etc...
June 7, 2017: World Journal of Gastroenterology: WJG
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