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Cholangiocarcinoma AND (immunotherapy OR CAR-T OR TILs)

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https://www.readbyqxmd.com/read/30056600/cytotoxic-activity-of-effector-t-cells-against-cholangiocarcinoma-is-enhanced-by-self-differentiated-monocyte-derived-dendritic-cells
#1
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...
July 28, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29936458/-in-vivo-study-of-natural-killer-nk-cell-cytotoxicity-against-cholangiocarcinoma-in-a-nude-mouse-model
#2
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
https://www.readbyqxmd.com/read/29859792/differential-association-between-circulating-lymphocyte-populations-with-outcome-after-radiation-therapy-in-subtypes-of-liver-cancer
#3
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
https://www.readbyqxmd.com/read/29843754/immune-checkpoint-therapy-in-liver-cancer
#4
REVIEW
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
https://www.readbyqxmd.com/read/29805739/prognostic-value-of-cd8cd45ro-tumor-infiltrating-lymphocytes-in-patients-with-extrahepatic-cholangiocarcinoma
#5
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
https://www.readbyqxmd.com/read/29790264/immune-responses-against-tumour-associated-antigen-derived-cytotoxic-t-lymphocyte-epitopes-in-cholangiocarcinoma-patients
#6
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)...
May 23, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29769134/advances-on-chimeric-antigen-receptor-modified-t-cell-therapy-for-oncotherapy
#7
REVIEW
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
https://www.readbyqxmd.com/read/29732001/prognostic-impact-of-programmed-cell-death-ligand-1-pd-l1-expression-and-its-association-with-epithelial-mesenchymal-transition-in-extrahepatic-cholangiocarcinoma
#8
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
https://www.readbyqxmd.com/read/29506673/desmoplastic-tumor-microenvironment-and-immunotherapy-in-cholangiocarcinoma
#9
REVIEW
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
https://www.readbyqxmd.com/read/29408314/fibroblast-growth-factor-receptor-inhibition-induces-loss-of-matrix-mcl1-and-necrosis-in-cholangiocarcinoma
#10
Ayano Kabashima, Petra Hirsova, Steven F Bronk, Matthew C Hernandez, Mark J Truty, Sumera Rizvi, Scott H Kaufmann, Gregory J Gores
BACKGROUND & AIMS: Myeloid cell leukemia 1 (MCL1), a prosurvival member of the BCL2 protein family, has a pivotal role in human cholangiocarcinoma (CCA) cell survival. We previously reported that fibroblast growth factor receptor (FGFR) signalling mediates MCL1-dependent survival of CCA cells in vitro and in vivo. However, the mode and mechanisms of cell death in this model were not delineated. METHODS: Human CCA cell lines were treated with the pan-FGFR inhibitor LY2874455 and the mode of cell death examined by several complementary assays...
June 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29238914/clinical-and-genetic-implications-of-dna-mismatch-repair-deficiency-in-biliary-tract-cancers-associated-with-lynch-syndrome
#11
Jordan M Cloyd, Yun Shin Chun, Naruhiko Ikoma, Jean Nicolas Vauthey, Tlhomas A Aloia, Amanda Cuddy, Miguel A Rodriguez-Bigas, Y Nancy You
PURPOSE: Patients with Lynch syndrome (LS) have a significantly elevated lifetime risk of developing biliary tract cancers (BTCs) compared to the general population. However, few studies have characterized the clinical characteristics, genetic features, or long-term outcomes of mismatch-repair deficient (dMMR) cholangiocarcinomas associated with LS. METHODS: A retrospective review of a prospectively maintained Familial High-Risk GI Cancer Clinic database identified all patients with BTCs evaluated from 2006 to 2016 who carried germline mutations in MLH1, MSH2, MSH6, or PMS2...
March 2018: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/29138340/phase-i-study-of-chimeric-antigen-receptor-modified-t-cells-in-patients-with-egfr-positive-advanced-biliary-tract-cancers
#12
Yelei Guo, Kaichao Feng, Yang Liu, Zhiqiang Wu, Hanren Dai, Qingming Yang, Yao Wang, Hejin Jia, Weidong Han
Purpose: This study is an expanded and parallel clinical trial of EGFR-specific chimeric antigen receptor-engineered autologous T (CART) cell immunotherapy (NCT01869166) to assess the safety and activity of CART-EGFR cell therapy in EGFR-positive advanced unresectable, relapsed/metastatic biliary tract cancers (BTC). Experimental Design: Patients with EGFR-positive (>50%) advanced unresectable, relapsed/metastatic BTCs were enrolled. Well-produced CART-EGFR cells were infused in a manner of dose escalation after the conditioning treatment with nab-paclitaxel (100-250 mg/m2 ) and cyclophosphamide (15-35 mg/kg)...
March 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29034817/enhanced-cytotoxic-activity-of-effector-t-cells-against-cholangiocarcinoma-by-dendritic-cells-pulsed-with-pooled-mrna
#13
Mutita Junking, Janya Grainok, Chutamas Thepmalee, Sopit Wongkham, Pa-Thai Yenchitsomanus
Cholangiocarcinoma is a malignancy of bile duct epithelia with an increasing in incidence rate worldwide. Surgery is the only curative treatment, while adjuvant chemotherapy and radiotherapy render poor responses. Cell-based immunotherapy is a potential strategy for cholangiocarcinoma treatment. However, variation of tumor antigens in cholangiocarcinoma leads to the ineffectiveness of cell-based immunotherapy. In this study, we examined the activation of effector T-cells by dendritic cells pulsed with protein lysate or total RNA from cholangiocarcinoma cell lines for their cytolytic activity against cholangiocarcinoma...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28808500/emerging-molecular-targets-and-therapy-for-cholangiocarcinoma
#14
REVIEW
Hamzeh Kayhanian, Elizabeth C Smyth, Chiara Braconi
Cholangiocarcinoma (CCA) is a rare cancer arising from the biliary tree with a poor prognosis and limited therapeutic options. Recent large scale molecular characterisation studies have identified recurrent genetic alterations in CCA which may be amenable to therapeutic targeting. In this review we explore the genomic landscape of CCA and examine results from trials of molecularly targeted agents and immunotherapy in this disease. Challenges in CCA diagnosis, treatment and trial design are discussed and we reflect on future directions which may lead to improved outcomes for CCA patients...
July 15, 2017: World Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28628842/matching-genomic-molecular-aberrations-with-molecular-targeted-agents-are-biliary-tract-cancers-an-ideal-playground
#15
REVIEW
Loic Verlingue, Antoine Hollebecque, Valérie Boige, Michel Ducreux, David Malka, Charles Ferté
Biliary tract cancers (BTCs) are a heterogeneous group of tumours with geographical discrepancies in terms of incidence and risk factors. However, a convergent genomic and epigenetic mutational landscape emerges from the genome-wide screens of BTCs in South East Asia, Latin America and in the Western World. Specificities are observed for some alterations and anatomical subtypes: frequent fibroblast growth factor receptor 2 (FGFR2) and isocitrate dehydrogenase 1/2 (IDH1/2) alterations are specific to intrahepatic cholangiocarcinomas (ICCs), whereas frequent ERBB2 oncogene alterations are specific to extrahepatic cholangiocarcinomas (ECCs) and gallbladder carcinomas (GBCs)...
August 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28445951/pd-l1-expression-in-perihilar-and-intrahepatic-cholangiocarcinoma
#16
Jacqueline Fontugne, Jérémy Augustin, Anaïs Pujals, Philippe Compagnon, Benoit Rousseau, Alain Luciani, Christophe Tournigand, Daniel Cherqui, Daniel Azoulay, Jean-Michel Pawlotsky, Julien Calderaro
Cholangiocarcinoma is an aggressive biliary neoplasm lacking effective therapeutic agents. Immunotherapies targeting the PD-L1/PD-1 immune checkpoint have shown encouraging results in solid and hematologic cancers in clinical trials. Response to these immunomodulators is correlated with PD-L1 expression. Our goal was to characterize PD-L1 expression in intra-hepatic (iCCA) and perihilar (pCCA) cholangiocarcinomas, and to correlate our results with clinicopathological features, density of tumor-infiltrating lymphocytes (TILs) and PD-1 expression...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28419539/pd-l1-expression-in-extrahepatic-cholangiocarcinoma
#17
Dirk Walter, Eva Herrmann, Andreas A Schnitzbauer, Stefan Zeuzem, Martin Leo Hansmann, Jan Peveling-Oberhag, Sylvia Hartmann
AIMS: To investigate the expression of the programmed cell death 1 (PD-1) receptor-programmed cell death ligand 1 (PD-L1) pathway and the clinicopathological characteristics in extrahepatic cholangiocarcinoma (eCCA). METHODS AND RESULTS: Tissue samples from patients with eCCA [n = 69; perihilar cholangiocarcinoma (CCA), 40; and distal CCA, 29] who underwent surgical resection in the period from 2007 to 2015 were evaluated for PD-1, PD-L1, CD3 and CD163 expression, and correlations with clinicopathological characteristics, including survival data, were determined...
September 2017: Histopathology
https://www.readbyqxmd.com/read/28410302/tumor-infiltrating-lymphocyte-therapy-and-neoantigens
#18
REVIEW
Paul F Robbins
The adoptive cell transfer (ACT) of autologous tumor-infiltrating lymphocytes has been shown to be effective at mediating tumor regression in more than half of patients with metastatic melanoma and in mediating long-term complete regression in approximately one fourth of all patients with this cancer. The success of this approach in patients with cholangiocarcinoma and colon cancer supports efforts to expand ACT therapies to treatment of patients bearing a wide array of cancer types. Recent improvements in deep sequencing of the patient cancers, combined with extensive immunological testing of autologous tumor-infiltrating lymphocytes, indicate that T cells targeting epitopes arising from nonsynonymous somatic mutations, termed neoantigens, play important roles in mediating many of the effective cancer immunotherapies seen in response to ACT...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28229078/systemic-therapy-of-cholangiocarcinoma
#19
REVIEW
Ruben R Plentz, Nisar P Malek
BACKGROUND: Cholangiocarcinoma (CC) is the second most common primary malignant liver disease. During the last decades, various novel therapies have been introduced in the field of oncology; nevertheless, the number of treatment options for CC is still limited. METHODS: In this article, current palliative chemotherapy concepts as well as new drug therapies are outlined. RESULTS: Gemcitabine and cisplatin are the standard treatment of care for patients with inoperable CC...
December 2016: Visceral Medicine
https://www.readbyqxmd.com/read/28218682/immune-mediated-therapies-for-liver-cancer
#20
REVIEW
Rajagopal N Aravalli, Clifford J Steer
In recent years, immunotherapy has gained renewed interest as an alternative therapeutic approach for solid tumors. Its premise is based on harnessing the power of the host immune system to destroy tumor cells. Development of immune-mediated therapies, such as vaccines, adoptive transfer of autologous immune cells, and stimulation of host immunity by targeting tumor-evasive mechanisms have advanced cancer immunotherapy. In addition, studies on innate immunity and mechanisms of immune evasion have enhanced our understanding on the immunology of liver cancer...
February 17, 2017: Genes
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