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Cholangiocarcinoma AND (immunotherapy OR CAR-T OR TILs)

Lorenza Rimassa, Nicola Personeni, Alessio Aghemo, Ana Lleo
Cholangiocarcinoma (CCA) is a deadly cancer of the biliary epithelium with limited therapeutic options. It is a heterogeneous group of cancer that could develop at any level from the biliary tree and is currently classified into intrahepatic, perihilar and distal based on its anatomical location. With incidence and mortality rates currently increasing, it is now the second most common type of primary liver cancer and represents up to 3% of all gastrointestinal malignancies. High-throughput genomics and epigenomics have greatly increased our understanding of CCA underlying biology, however its pathogenesis remains largely unknown...
March 9, 2019: Journal of Autoimmunity
Fei Yu, Lei Gong, Zheng Mo, Wenran Wang, Meilong Wu, Jianghui Yang, Qiongqiong Zhang, Li Li, Jingjing Yao, Jiahong Dong
Immunotherapy might be an effective treatment in extrahepatic cholangiocarcinoma (eCCA), a tumor with extremely limited therapeutic options. Our study is to characterize the programmed death ligand-1 (PD-L1) protein expression and cancer microenvironment profiles in surgically resected eCCA samples. PD-L1 positivity was observed on tumor cells (32.3%) as well as on tumor-associated macrophages (74.2%). PD-L1 expression by eCCA correlated significantly with immune parameters such as intra-tumoral CD3+ tumor infiltrating lymphocytes (TILs) density (P = 0...
February 15, 2019: Bioscience Trends
Mohammed Alnaggar, Yan Xu, Jingxia Li, Junyi He, Jibing Chen, Man Li, Qingling Wu, Li Lin, Yingqing Liang, Xiaohua Wang, Jiawei Li, Yi Hu, Yan Chen, Kecheng Xu, Yangzhe Wu, Zhinan Yin
BACKGROUND: Cholangiocarcinoma (CCA) is a highly aggressive and fatal tumor. CCA occurs in the epithelial cells of bile ducts. Due to increasing incidences, CCA accounts for 3% of all gastrointestinal malignancies. In addition to comprehensive treatments for cancer, such as surgery, chemotherapy, and radiotherapy, during the past few years, cellular immunotherapy has played an increasingly important role. As a result of our research, we have discovered the γδ T cell-based immunotherapy for CCA...
February 8, 2019: Journal for Immunotherapy of Cancer
Xiao Chen, Numan Kutaiba, Brian Ngo, Mark Goodwin
INTRODUCTION: To evaluate the histopathological and safety outcomes of indeterminate lesions in patients at high risk for developing hepatocellular carcinoma (HCC) who underwent ultrasound-guided biopsies. METHODS: Ultrasound-guided targeted liver biopsies for indeterminate lesions performed in a 10-year period at our institution were reviewed retrospectively for lesion characteristics, biopsy techniques, histopathological results and post procedural complications...
January 16, 2019: Journal of Medical Imaging and Radiation Oncology
Mark Kriegsmann, Stephanie Roessler, Katharina Kriegsmann, Marcus Renner, Rémi Longuespée, Thomas Albrecht, Moritz Loeffler, Stephan Singer, Arianeb Mehrabi, Monika Nadja Vogel, Anita Pathil, Bruno Köhler, Christoph Springfeld, Christian Rupp, Karl Heinz Weiss, Benjamin Goeppert
BACKGROUND: Cholangiocarcinoma (CCA) may arise in the intra- or extrahepatic biliary tract and is associated with a poor prognosis. Despite recent advances, to date there is still no established targeted therapeutic approach available. Non-surgical therapeutic agents are urgently needed, as most patients are non-eligible to surgical resection. Anti-PD-L1 therapy prevents cancer cells from evading the immune system and has emerged as a new treatment option in several cancer entities. Recently, PD-L1 expression has been analyzed in comparably small CCA patient cohorts...
January 15, 2019: BMC Cancer
R C Liu, G Consuegra, S Chou, P Fernandez Peñas
Vitiligo-like depigmentation (VLD) is a characteristic cutaneous event described in patients with metastatic malignant melanoma receiving treatment with immune checkpoint inhibitors. We report the onset of VLD in three patients with other cancer types (cholangiocarcinoma, renal cell carcinoma and squamous cell carcinoma) following treatment with immunotherapy (combination pembrolizumab and nivolumab for the first, and pembrolizumab for the other two cancer types). Cases of VLD have not been reported previously in patients treated for any of these cancers, to our knowledge...
January 7, 2019: Clinical and Experimental Dermatology
Chu-Yu Jing, Yi-Peng Fu, Jin-Long Huang, Mei-Xia Zhang, Yong Yi, Wei Gan, Xin Xu, Hu-Jia Shen, Jia-Jia Lin, Su-Su Zheng, Juan Zhang, Jian Zhou, Jia Fan, Zheng-Gang Ren, Shuang-Jian Qiu, Bo-Heng Zhang
BACKGROUND: Fibrotic tumor stroma (FTS) has been implicated in cancer promotion in several neoplasms. The histological features of FTS are convenient and easily accessible in clinical routine in intrahepatic cholangiocarcinoma (ICC) specimens. The goal of this study was to explore prognostic impacts of the quantity and maturity of FTS on surgical ICC patients. Moreover, we aimed to propose an efficient prognostic nomogram for postoperative ICC patients. MATERIALS AND METHODS: The clinical profiles of 154 consecutive postoperative ICC patients were retrospectively analyzed...
December 2018: Oncologist
Angela Lamarca, Jorge Barriuso, Mairéad G McNamara, Juan W Valle
Biliary tract cancers (BTCs), including cholangiocarcinoma, gallbladder cancer and ampullary cancers, are poor-prognosis malignancies. Most patients are diagnosed with advanced disease, when treatment is limited to palliative chemotherapy. First line chemotherapy is usually administered in the form of cisplatin and gemcitabine. Benefit from second line chemotherapy is still to be confirmed. Even though new systemic treatment targets have been recognised, especially in patients with intrahepatic cholangiocarcinoma (e...
November 2018: Cancer Treatment Reviews
Da Hye Kim, Byeong Nam Im, Hee Sook Hwang, Kun Na
To improve the therapeutic efficacy of gemcitabine (GEM) as an anticancer drug for bile duct cancer, GEM-loaded liposomes (GDPPL) prepared from a photosensitizer-conjugated lipid were investigated regarding the drug release kinetics, photodynamic therapy (PDT) efficacy, and immunomodulatory effects. The release rate of GEM from the liposomes was improved approximately 2-fold compared to non-laser irradiation groups due to lipid disruption by reactive oxygen species produced from the activated photosensitizer upon laser irradiation...
August 23, 2018: Biomaterials
Antonio Pellino, Fotios Loupakis, Massimiliano Cadamuro, Vincenzo Dadduzio, Matteo Fassan, Maria Guido, Umberto Cillo, Stefano Indraccolo, Luca Fabris
Cholangiocarcinoma is one of the epithelial cancers with the poorest prognosis and the narrowest therapeutic choice in humans. Compared with other cancer types, cholangiocarcinoma has been often neglected by oncology and liver research studies, thereby leaving many issues unsolved. Apart from the early and marked aggressiveness, one of the main reasons of the still unsatisfying clinical management of cholangiocarcinoma is its wide tumor heterogeneity needing more than other diseases a 'precision medicine' approach...
2018: Translational Gastroenterology and Hepatology
Amit Mahipal, Anuhya Kommalapati, Sri Harsha Tella, Alexander Lim, Richard Kim
Surgical resection remains the mainstay of potentially curative treatment in the early stages of cholangiocarcinoma, whereas for the advanced stage, systemic chemotherapeutics and experimental targeted therapies are the primary treatment options. The molecular heterogeneity of the tumor is based on location, liver dysfunction, and relative rarity of the disease and confers challenges for clinical trial enrollment. The advancements in the understanding of molecular pathogenesis of cholangiocarcinoma have led to the development of targeted therapies that are currently being evaluated in the clinical trials...
September 2018: Expert Opinion on Investigational Drugs
Aussara Panya, Chutamas Thepmalee, Nunghathai Sawasdee, Jatuporn Sujjitjoon, Nattaporn Phanthaphol, Mutita Junking, Sopit Wongkham, Pa-Thai Yenchitsomanus
Cholangiocarcinoma (CCA) is a cancer of the bile ducts that is associated with poor prognosis and poor treatment outcome. Approximately one-third of CCA patients can undergo surgery, but the recurrence rate is high and chemotherapy often cannot satisfactorily prolong survival. Cellular immunotherapy based on adoptive T-cell transfer is a potential treatment for CCA; however, the development of this technology and the search for an appropriate tumor-associated antigen are still ongoing. To enhance the cytotoxic activity of effector T cells against CCA, we developed self-differentiated monocyte-derived dendritic cells (SD-DC) presenting cAMP-dependent protein kinase type I-alpha regulatory subunit (PRKAR1A), which is an overexpressed protein that plays a role in the regulation of tumor growth to activate T cells for CCA cell killing...
October 2018: Cancer Immunology, Immunotherapy: CII
In Hye Jung, DO Hee Kim, DA Kyung Yoo, Sun Young Baek, Seong Hoon Jeong, Dawoon E Jung, Seung Woo Park, Yong-Yoon Chung
BACKGROUND/AIM: Natural killer (NK) cells are one of the lymphocytes clinically used for various cancer types. Cytotoxicity of NK cells to cholangiocarcinoma (CC), however, has not yet been studied. Nor NK cell therapy against CC has been clinically applied. In this study, relevance of NK cell therapy for anti-tumor efficacy against CC was pre-clinically investigated. MATERIALS AND METHODS: Human HuCCT-1 cells, an intrahepatic CC cell line, were xenografted into nude mice...
July 2018: In Vivo
Clemens Grassberger, Theodore S Hong, Tai Hato, Beow Y Yeap, Jennifer Y Wo, Mark Tracy, Thomas Bortfeld, John A Wolfgang, Christine E Eyler, Lipika Goyal, Jeffrey W Clark, Christopher H Crane, Eugene J Koay, Mark Cobbold, Thomas F DeLaney, Rakesh K Jain, Andrew X Zhu, Dan G Duda
PURPOSE: Irradiation may have significant immunomodulatory effects that impact tumor response and could potentiate immunotherapeutic approaches. The purposes of this study were to prospectively investigate circulating lymphoid cell population fractions during hypofractionated proton therapy (HPT) in blood samples of liver cancer patients and to explore their association with survival. METHODS AND MATERIALS: We collected serial blood samples before treatment and at days 8 and 15 of HPT from 43 patients with liver cancer-22 with hepatocellular carcinoma (HCC) and 21 with intrahepatic cholangiocarcinoma (ICC)-enrolled in a phase 2 clinical trial...
August 1, 2018: International Journal of Radiation Oncology, Biology, Physics
Feng Xu, Tianqiang Jin, Yuwen Zhu, Chaoliu Dai
Immune checkpoints include stimulatory and inhibitory checkpoint molecules. In recent years, inhibitory checkpoints, including cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death ligand 1 (PD-L1), have been identified to suppress anti-tumor immune responses in solid tumors. Novel drugs targeting immune checkpoints have succeeded in cancer treatment. Specific PD-1 blockades were approved for treatment of melanoma in 2014 and for treatment of non-small-cell lung cancer in 2015 in the United States, European Union, and Japan...
May 29, 2018: Journal of Experimental & Clinical Cancer Research: CR
Richard Kim, Domenico Coppola, Emilie Wang, Young Doo Chang, Yuhree Kim, Daniel Anaya, Dae Won Kim
Cholangiocarcinoma is a malignancy arising from the biliary tract epithelial cells with poor prognosis. Tumor infiltrating lymphocytes (TIL)s and programmed cell death receptor ligand 1 (PD-L1) have a prognostic impact in various solid tumors. We aimed to investigate TILs and PD-L1 expression and their clinical relevance in cholangiocarcinoma. Tumor samples from 44 patients with resected and histologically verified extrahepatic cholangiocarcinoma were evaluated for CD8, CD45RO and PD-L1 expression, and their correlations with clinicopathological data and survival data were analyzed...
May 4, 2018: Oncotarget
Akihiko Kida, Eishiro Mizukoshi, Toshikatsu Tamai, Takeshi Terashima, Masaaki Kitahara, Kuniaki Arai, Tatsuya Yamashita, Kazumi Fushimi, Masao Honda, Shuichi Kaneko
BACKGROUND & AIMS: Immunotherapy is a promising treatment option for cholangiocarcinoma. We compared cytotoxic T lymphocyte (CTL) responses against several tumour-associated antigen (TAA)-derived epitopes in cholangiocarcinoma patients to identify candidate epitopes for immunotherapy. METHODS: Twenty-six TAAs were selected, and the expression of TAAs in 6 cholangiocarcinoma cell lines and 9 specimens were measured using real-time polymerase chain reaction (PCR)...
November 2018: Liver International: Official Journal of the International Association for the Study of the Liver
Yanyu Pang, Xiaoyang Hou, Chunsheng Yang, Yanqun Liu, Guan Jiang
Tumor treatment is still complicated in the field of medicine. Tumor immunotherapy has been the most interesting research field in cancer therapy. Application of chimeric antigen receptor T (CAR-T) cell therapy has recently achieved excellent clinical outcome in patients, especially those with CD19-positive hematologic malignancies. This phenomenon has induced intense interest to develop CAR-T cell therapy for cancer, especially for solid tumors. However, the performance of CAR-T cell treatment in solid tumor is not as satisfactory as that in hematologic disease...
May 16, 2018: Molecular Cancer
Takashi Ueno, Takahiro Tsuchikawa, Kanako C Hatanaka, Yutaka Hatanaka, Tomoko Mitsuhashi, Yoshitsugu Nakanishi, Takehiro Noji, Toru Nakamura, Keisuke Okamura, Yoshihiro Matsuno, Satoshi Hirano
Extrahepatic cholangiocarcinoma (eCCA) has a poor prognosis. Although the possibility of immunotherapy has been studied, immune checkpoint molecules such as programmed death ligand 1 (PD-L1) in eCCA are not well understood. Epithelial-mesenchymal transition (EMT) has recently been shown to regulate PD-L1 expression. Our aims were to assess the clinicopathological significance of tumor-infiltrating lymphocytes (TILs) and tumor PD-L1 expression in eCCA and to compare these immune responses with EMT marker expression...
April 13, 2018: Oncotarget
Dan Høgdall, Monika Lewinska, Jesper B Andersen
Cholangiocarcinoma (CCA) is a dismal disease which often is diagnosed at a late stage where the tumor is locally advanced, metastatic, and, as a result, is associated with low resectability. The heterogeneity of this cancer type is a major reason why the majority of patients fail to respond to therapy, and surgery remains their only curative option. Among patients who undergo surgical intervention, such tumors typically recur in 50% of cases within 1year. Thus, CCA is among the most aggressive and chemoresistant malignancies...
March 2018: Trends in Cancer
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