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Liver cancer immunotherapy

Wei Tian, Jun Ma, Ruyi Shi, Chongren Ren, Jiefeng He, Haoliang Zhao
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. γδ T cells have been revealed to be promising candidates for immunotherapy in patients with HCC. However, the use of these cells in clinical practice has been demonstrated to be challenging. In the present study, γδ T cells isolated from the peripheral blood of patients with HCC (n=83) and healthy donors (n=15) were characterized. Flow cytometry was used to analyze the proportion, phenotype, tumor-killing capacity and cytokine secretion of regulatory T cells (Tregs) and γδ T17 cells in peripheral blood samples prior to and following amplification...
April 2018: Oncology Letters
Fen Huang, Bo Wang, Jiangzheng Zeng, Shenggang Sang, Junhua Lei, Yanda Lu
Programmed cell death-1 (PD-1) is an oncogene associated with suppressing proliferation and cytokine production of T cells in the progression of liver cancer. microRNAs (miRs) regulate gene expression via specific binding to the target 3'untranslated region of mRNA. In the present study, miR-374b was indicated to interact with PD-1 and affect the tumor-targeting capacity of cytokine-induced killer (CIK) cells. miR-374b inhibitor significantly increased PD-1 expression in CIK cells. A synthetic small interfering (si)RNA targeting PD-1 was employed to silence the expression level of PD-1 in CIK cells...
April 2018: Oncology Letters
Kevin Zarrabi, Shenhong Wu
BACKGROUND: Nivolumab is approved for the treatment of many cancers. This meta-analysis was conducted to determine the risk of hepatotoxicity with nivolumab therapy. METHODS: An analysis from all phase I-III clinical trials up to December 2016 examining nivolumab was conducted. Data on elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were extracted from the safety profiles of each trial. Incidence and relative risk (RR) were calculated using random- or fixed-effects models with 95% confidence intervals (CIs)...
March 14, 2018: Oncology
Xiao-Zhen Kang, Xue-Ran Guo, Bin-Bing Chen, Tian-Ying Zhang, Quan Yuan, Pei-Jer Chen, Jun Zhang, Ning-Shao Xia
There are estimated 248 million individuals worldwide persistently infected with hepatitis B virus (HBV), if without timely and effective treatment, about 25%-40% of whom would develop to liver cancer, cirrhosis or other HBV related end-stage liver diseases. Our previously study has reported a unique antibody named E6F6, that recognizes HBsAg-aa119-125 and is capable of prolonged suppression of HBsAg and HBV DNA levels in mice. In this study, data revealed that the consecutive E6F6 treatments can not only effectively inhibit HBV viremia, but also significantly reduce HBV-induced hepatocarcinogenesis in DEN-treated HBV-Tg mice...
March 13, 2018: Human Vaccines & Immunotherapeutics
Jesper B Andersen
No abstract text is available yet for this article.
February 2018: Hepatobiliary Surgery and Nutrition
Kyosuke Yamanishi, Keiichiro Mukai, Takuya Hashimoto, Kaoru Ikubo, Keiji Nakasho, Yosif El-Darawish, Wen Li, Daisuke Okuzaki, Yuko Watanabe, Tetsu Hayakawa, Hiroshi Nojima, Hiromichi Yamanishi, Haruki Okamura, Hisato Matsunaga
BACKGROUND: The cytokine interleukin-18 was originally identified as an interferon-γ-inducing proinflammatory factor; however, there is increasing evidence to suggest that it has non-immunological effects on physiological functions. We previously investigated the potential pathophysiological relationship between interleukin-18 and dyslipidemia, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis, and suggested interleukin-18 as a possible novel treatment for not only these diseases but also for cancer immunotherapy...
March 7, 2018: Journal of Translational Medicine
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
Ziwei Guo, Chao Meng, Xing Wei, Chuanhao Tang, Jun Liang
The outcome of small cell lung cancer (SCLC) patients is poor because rapid metastasis develops after first-line chemotherapy and few drugs are available for second-line chemotherapy. The median survival rate has not significantly changed in recent years. In this report, we discuss the case of a 71-year-old Chinese female non-smoker diagnosed with extensive-stage SCLC who was treated with nivolumab for a short period and obtained a prolonged clinical benefit. We report the clinical history, clinical features, potential mechanism, benefits, and the best therapeutic window...
March 2, 2018: Thoracic Cancer
Lena Tienken, Natascha Drude, Isabell Schau, Oliver H Winz, Achim Temme, Elmar Weinhold, Felix M Mottaghy, Agnieszka Morgenroth
In pretargeted radio-immunotherapy, the gradual administration of a non-radioactive tumor antigen-addressing antibody-construct and the subsequent application of a radioactive labeled, low molecular weight substance enable a highly effective and selective targeting of tumor tissue. We evaluated this concept in prostate stem cell antigen (PSCA)-positive cancers using the antigen-specific, biotinylated single chain antibody scFv(AM1)-P-BAP conjugated with tetrameric neutravidin. To visualize the systemic biodistribution, a radiolabeled biotin was injected to interact with scFv(AM1)-P-BAP/neutravidin conjugate...
February 28, 2018: Scientific Reports
Yih-Lin Chung, Mei-Ling Wu
Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated lymphoepithelioma. The aim of the present study was to characterize the homogeneity and distinctness of the T-cell repertoires within and between primary and metastatic NPCs. We used ultra-deep sequencing of the hypervariably rearranged antigen-binding CDR3 regions of T-cell receptor beta (TCRbeta ) to comprehensively profile the T-cell repertoires in NPC patients receiving definitive chemoradiotherapy with long-term follow-up. We observed not only various spatially heterogeneous patient-specific TCRbeta clone compositions that changed with time but also several commonly enriched TCRbeta subclones that were constantly shared between primary NPCs in the head and neck regions, locally recurrent tumors after treatment, and later-developed distant metastatic tumors in the liver, lung and bone...
February 22, 2018: International Journal of Cancer. Journal International du Cancer
Lin Yu, Ying Lu, Yuqin Yao, Yu Liu, Yuxi Wang, Qinhuai Lai, Ruirui Zhang, Wenting Li, Ruixue Wang, Yuyin Fu, Yiran Tao, Shuli Yi, Lantu Gou, Ligong Chen, Jinliang Yang
Small cell lung cancer (SCLC) is of a highly invasive and metastatic lung cancer subtype and there had not been effective targeted therapies. CD56, a cell surface marker highly expressed on most SCLC, is a promising therapeutic target for treatment of this aggressive cancer. In this study, we generated a novel anti-CD56 antibody named promiximab, characterized by high affinity, internalization and tumor specificity. Then, the promiximab was conjugated with a potent DNA alkylating agent duocarmycin via reduced interchain disulfides to yield the promiximab-Duocarmycin (promiximab-DUBA) conjugates...
January 12, 2018: Oncotarget
Eleonora De Martin, Jean-Marie Michot, Barbara Papouin, Stéphane Champiat, Christine Mateus, Olivier Lambotte, Bruno Roche, Teresa Maria Antonini, Audrey Coilly, Salim Laghouati, Caroline Robert, Aurélien Marabelle, Catherine Guettier, Didier Samuel
BACKGROUND & AIMS: Immunotherapy for metastatic cancer may be complicated by the onset of hepatic immune-related adverse events (IRAEs). This study compared hepatic IRAEs associated with anti-PD-1/PD-L1 and anti-CTLA-4 monoclonal antibodies (mAb). METHODS: Among 536 patients treated with anti-PD-1/PD-L1 or CTLA-4 immunotherapies, 19 (3.5%) were referred to the liver unit for grade ≥ 3 hepatitis. Among 16 included patients: 9 received anti-PD-1/PD-L1 while 7 received anti-CTLA-4 mAb, in monotherapy or in combination with anti-PD-1...
February 7, 2018: Journal of Hepatology
Qian Yang, Michael H Roehrl, Julia Y Wang
We hypothesized that cancer tissue immunogens - antigens capable of inducing specific antibody production in patients - are promising targets for development of precision diagnostics and humoral immunotherapies. We developed an innovative immuno-proteomic strategy and identified new immunogenic markers of colon cancer. Proteins from cancers and matched normal tissues were separated by 2D gel electrophoresis and blotted with serum antibodies from the same patients. Antibody-reactive proteins were sequenced by mass spectrometry and validated by Western blotting and immunohistochemistry...
January 9, 2018: Oncotarget
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
Yoh Zen, Matthew M Yeh
The adverse effects of immune checkpoint inhibitors in various organs may be attributed to immune-mediated processes triggered by disrupted self-tolerance; however, it remains unclear whether they are similar or dissimilar to classic organ-specific autoimmune diseases. The present study aimed to compare clinicopathologic features between checkpoint inhibitor-induced liver injury and acutely presenting autoimmune hepatitis or idiosyncratic drug-induced liver injury. Seven patients treated with nivolumab (n = 5) or ipilimumab (n = 2) presented with liver dysfunction a median of 41 days (range 21-120) after the initiation of immunotherapy...
February 5, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Clément Korenbaum, Laure Pierard, Alicia Thiéry, Fleur Story, Véronique Lindner, Hervé Lang, Jean-Emmanuel Kurtz, Philippe Barthélémy
INTRODUCTION: Metastatic renal cell carcinoma (RCC) with a sarcomatoid component is a rare disease associated with a poor prognosis. We report the outcomes of 47 patients with metastatic sarcomatoid RCC (SRCC) treated with different modalities including chemotherapy, tyrosine kinase inhibitors, or immunotherapy over 2 decades in a French cancer center. Furthermore, we assessed the validity of prognostic scores in this subset of RCC. PATIENTS AND METHODS: Patients were retrospectively identified from the database of the pathology department of the University Hospital of Strasbourg...
December 28, 2017: Clinical Genitourinary Cancer
Grace Mahlbacher, Louis T Curtis, John Lowengrub, Hermann B Frieboes
BACKGROUND: Immuno-oncotherapy has emerged as a promising means to target cancer. In particular, therapeutic manipulation of tumor-associated macrophages holds promise due to their various and sometimes opposing roles in tumor progression. It is established that M1-type macrophages suppress tumor progression while M2-types support it. Recently, Tie2-expressing macrophages (TEM) have been identified as a distinct sub-population influencing tumor angiogenesis and vascular remodeling as well as monocyte differentiation...
January 30, 2018: Journal for Immunotherapy of 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
Qi Liu, Hongda Zhu, Karthik Tiruthani, Limei Shen, Fengqian Chen, Keliang Gao, Xueqiong Zhang, Lin Hou, Degeng Wang, Rihe Liu, Leaf Huang
Development of an effective treatment against advanced tumors remains a major challenge for cancer immunotherapy. Approximately 50% of human melanoma is driven by B-Raf proto-oncogene mutation (BRAF-mutant). Tumors with such mutation are desmoplastic, highly immunosuppressive, and often resistant to immune checkpoint therapies. We have shown that immunotherapy mediated by low dose doxorubicin-induced immunogenic cell death was only partially effective for this type of tumor, and not effective in long-term inhibition of tumor progression...
January 25, 2018: ACS Nano
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