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Pancreatic cancer immunotherapy

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https://www.readbyqxmd.com/read/28965867/cxcr5-cd8-t-cells-potently-infiltrate-pancreatic-tumors-and-present-high-functionality
#1
Minghui Bai, Youwei Zheng, Haichao Liu, Baowei Su, Yong Zhan, Hua He
Despite continued improvement in conventional therapy, pancreatic cancer continues to be one of the deadliest tumors worldwide with abysmal 5-year survival rate. New immunotherapeutic strategies that aim at improving antitumor cytotoxic CD8(+) T cell responses are being developed in solid tumors. To assist the development of immunotherapies, we investigated the CD8(+) T cells in pancreatic cancer patients. Compared to healthy individuals, pancreatic cancer patients presented a significant enrichment in the frequency of CD8(+)CXCR5(+) T cells...
September 28, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28945842/immunotherapy-in-pancreatic-ductal-adenocarcinoma-an-emerging-entity
#2
I H Sahin, G Askan, Z I Hu, E M O'Reilly
The genomic-plasticity of the immune system creates a broad immune repertoire engaged to tackle cancer cells. Promising clinical activity has been observed with several immune therapy strategies in solid tumors including melanoma, lung, kidney and bladder cancers, albeit as yet immunotherapy-based treatment approaches in pancreatic ductal adenocarcinoma (PDAC) remain to have proven value. While translational and early clinical studies have demonstrated activation of antitumor immunity, most recent late-phase clinical trials have not confirmed the early promise in PDAC except in MSI-High PDAC patients...
September 4, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28932079/nano-albumin-bound-paclitaxel-in-pancreatic-cancer-current-evidences-and-future-directions
#3
REVIEW
Guido Giordano, Massimo Pancione, Nunzio Olivieri, Pietro Parcesepe, Marianna Velocci, Tania Di Raimo, Luigi Coppola, Giuseppe Toffoli, Mario Rosario D'Andrea
Pancreatic cancer (PDAC) is an aggressive and chemoresistant disease, representing the fourth cause of cancer related deaths in western countries. Majority of patients have unresectable, locally advanced or metastatic disease at time of diagnosis and the 5-year survival rate in these conditions is extremely low. For more than a decade gemcitabine has been the cornerstone of metastatic PDAC treatment, although survival benefit was very poor. PDAC cells are surrounded by an intense desmoplastic reaction that may create a barrier to the drugs penetration within the tumor...
August 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28928888/potential-roles-of-peripheral-dopamine-in-tumor-immunity
#4
REVIEW
Xiang Zhang, Qiaofei Liu, Quan Liao, Yupei Zhao
Recent years, immunotherapy has turned out to be a promising strategy against tumors. Peripheral dopamine (DA) has important roles in immune system among tumor patients. Accumulated reports demonstrate variable expression and distribution of DA receptors (DRs) in diverse immune cells. Interestingly, peripheral DA also involves in tumor progression and it exerts anticancer effects on immunomodulation, which includes inflammasomes in cancer, function of immune effector cells, such as T lymphocytes, myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs) and natural killer (NK) cells...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28917654/the-anticancer-functions-of-rig-i-like-receptors-rig-i-and-mda5-and-their-applications-in-cancer-therapy
#5
REVIEW
Yuanbing Wu, Xinqiang Wu, Longhuo Wu, Xiangcai Wang, Zhiping Liu
Cancer is a major cause of death worldwide, and its incidence and mortality continuously increase in China. Nowadays, cancer heavily influences our health and constitutes enormous burden on society and families. Although there are many tools for cancer treatment, but the overall therapeutic effect is poor. In addition, cancer cells often develop resistance to therapy due to defective cell death or immune escape mechanisms. Therefore, it is a promising way for cancer treatment to effectively activate apoptosis and conquer immunosuppression...
August 31, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28893836/immunotherapy-against-endocrine-malignancies-immune-checkpoint-inhibitors-lead-the-way
#6
Lucas Leite Cunha, Marjory Alana Marcello, Vinicius Rocha-Santos, Laura Sterian Ward
Immune checkpoint inhibitors are agents that act by inhibiting the mechanisms of immune escape displayed by various cancers. The success of immune checkpoint inhibitors against several tumors has promoted a new treatment strategy in clinical oncology, and this has encouraged physicians to increase the number of patients who receive the immune checkpoint therapy. In the present article, we review the main concepts regarding immune checkpoint mechanisms and how cancer disrupts them to undergo immune escape. In addition, we describe the most essential concepts related to immune checkpoint inhibitors...
September 11, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28871458/percutaneous-irreversible-electroporation-combined-with-allogeneic-natural-killer-cell-immunotherapy-for-patients-with-unresectable-stage-iii-iv-pancreatic-cancer-a-promising-treatment
#7
Mao Lin, Shuzhen Liang, Xiaohua Wang, Yinqing Liang, Mingjie Zhang, Jibing Chen, Lizhi Niu, Kecheng Xu
PURPOSE: This study was attempted to investigate the safety and clinical efficacy of percutaneous irreversible electroporation combined with allogeneic natural killer cell therapy for treating stage III/IV pancreatic cancer, evaluate median progression-free survival (PFS), and overall survival (OS). METHODS: Between March 2016 and February 2017, we enrolled 67 patients who met the enrollment criteria. According to the latest NCCN Guidelines, the patients were divided into stage III (35 patients, 16 patients received only irreversible electroporation (IRE) and 19 patients received IRE-NK: 8 patients underwent one course NK and 11 patients underwent ≥3 courses) and stage IV (32 patients, 14 patients received only IRE and 18 patients received IRE-NK: 8 patients underwent one course NK and 10 patients underwent ≥3 courses)...
September 4, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28860827/clinical-applications-of-dendritic-cells-cytokine-induced-killer-cells-mediated-immunotherapy-for-pancreatic-cancer-an-up-to-date-meta-analysis
#8
Yucai Zhang, Xiaorui Zhang, Anqi Zhang, Ke Li, Kai Qu
PURPOSE: This study aimed to systematically evaluate the efficacy and safety of dendritic cells-cytokine-induced killer (DC-CIK) cells immunotherapy in treating pancreatic cancer (PC) patients. METHODS: Data were collected from published articles of clinical trials. Databases including Web of Science, EMBASE, PubMed, Cochrane Library, Wanfang, and CNKI were searched. The main outcome measures in this research included the overall response rate (ORR), disease control rate (DCR), overall survival (OS), patients' quality of life (QoL), immune function, and adverse events...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28856392/ctla-4-cd80-pathway-regulates-t-cell-infiltration-into-pancreatic-cancer
#9
Fee Bengsch, Dawson M Knoblock, Anni Liu, Florencia McAllister, Gregory L Beatty
The ability of some tumors to exclude effector T cells represents a major challenge to immunotherapy. T cell exclusion is particularly evident in pancreatic ductal adenocarcinoma (PDAC), a disease where blockade of the immune checkpoint molecule CTLA-4 has not produced significant clinical activity. In PDAC, effector T cells are often scarce within tumor tissue and confined to peritumoral lymph nodes and lymphoid aggregates. We hypothesized that CTLA-4 blockade, despite a lack of clinical efficacy seen thus far in PDAC, might still alter T cell immunobiology, which would have therapeutic implications...
August 30, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28845161/targeting-cancer-stem-cells-and-their-niche-current-therapeutic-implications-and-challenges-in-pancreatic-cancer
#10
REVIEW
Jiangang Zhao, Jiahui Li, Hans A Schlößer, Felix Popp, Marie Christine Popp, Hakan Alakus, Karl-Walter Jauch, Christiane J Bruns, Yue Zhao
Cancer stem cells (CSCs) have been identified as a subpopulation of stem-like cancer cells with the ability of self-renewal and differentiation in hematological malignancies and solid tumors. Pancreatic cancer is one of the most lethal cancers worldwide. CSCs are thought to be responsible for cancer initiation, progression, metastasis, chemoresistance, and recurrence in pancreatic cancer. In this review, we summarize the characteristics of pancreatic CSCs and discuss the mechanisms involved in resistance to chemotherapy, the interactions with the niche, and the potential role in cancer immunoediting...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28839967/yes-associated-protein-and-immunosuppressive-microenvironment-in-pancreatic-cancer-development-a-new-strategy-to-improve-immunotherapy-efficacy
#11
EDITORIAL
Rossana Berardi, Alessandro Bittoni
No abstract text is available yet for this article.
July 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28835191/t-cell-optimization-for-the-treatment-of-pancreatic-cancer
#12
Fang Liu, Muhammad Wasif Saif
Pancreatic cancer remains a deadly disease despite advances in surgery, chemotherapy, and radiation therapy. Treatment failure is likely due to intense chemoresistance and immunosuppression. Therefore, new treatment paradigms are urgently needed. Immunotherapy, particularly adoptive T cell transfer, is a highly-personalized therapy that involves the isolation and ex vivo expansion of tumor-specific T cells before administration to cancer-bearing hosts. Areas covered: This review summarizes different strategies of adoptive T cell therapy and their application in pancreatic cancer treatment...
August 23, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28826722/pd-1-pd-l1-and-immunotherapy-for-pancreatic-cancer
#13
REVIEW
Mengyu Feng, Guangbing Xiong, Zhe Cao, Gang Yang, Suli Zheng, Xujun Song, Lei You, Lianfang Zheng, Taiping Zhang, Yupei Zhao
Therapy that targets programmed death 1 or programmed death 1 ligand 1 (PD-1/PD-L1), which are known as immune checkpoints, has been recently rapidly developing as oncotherapy for various carcinomas. However, this therapy has a poor effect on the treatment of pancreatic cancer with PD-1/PD-L1 blockade monotherapy. In this review, the development and limitations of anti-PD-1/PD-L1 monotherapy in pancreatic cancer are discussed. We then consider the underlying mechanism of anti-PD-1/PD-L1 monotherapy failure, combination strategies overcoming resistance to anti-PD-1/PD-L1 immunotherapy and the prospect of targeting PD-1/PD-L1 for the immunotherapy of pancreatic cancer...
October 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28811976/long-lived-pancreatic-ductal-adenocarcinoma-slice-cultures-enable-precise-study-of-the-immune-microenvironment
#14
Xiuyun Jiang, Y David Seo, Jae Hyuck Chang, Andrew Coveler, Eslam N Nigjeh, Sheng Pan, Florencia Jalikis, Raymond S Yeung, Ian N Crispe, Venu G Pillarisetty
Pancreatic ductal adenocarcinoma (PDA) remains a deadly disease that is rarely cured, despite many recent successes with immunotherapy for other malignancies. As the human disease is heavily infiltrated by effector T cells, we postulated that accurately modeling the PDA immune microenvironment would allow us to study mechanisms of immunosuppression that could be overcome for therapeutic benefit. Using viable precision-cut slices from fresh PDA, we developed an organotypic culture system for this purpose. We confirmed that cultured slices maintain their baseline morphology, surface area, and microenvironment after at least 6 d in culture, and demonstrated slice survival by MTT assay and by immunohistochemistry staining with Ki-67 and cleaved-Caspase-3 antibodies...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811962/an-ror1-bi-specific-t-cell-engager-provides-effective-targeting-and-cytotoxicity-against-a-range-of-solid-tumors
#15
Satyen Harish Gohil, Solange Rosa Paredes-Moscosso, Micaela Harrasser, Marzia Vezzalini, Aldo Scarpa, Emma Morris, Andrew M Davidoff, Claudio Sorio, Amit Chunilal Nathwani, Marco Della Peruta
We have developed a humanized bi-specific T-cell engager (BiTE) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1), a cell surface antigen present on a range of malignancies and cancer-initiating cells. Focusing initially on pancreatic cancer, we demonstrated that our ROR1 BiTE results in T cell mediated and antigen-specific cytotoxicity against ROR1-expressing pancreatic cancer cell lines in vitro at exceedingly low concentrations (0.1 ng/mL) and low effector to target ratios. Our BiTE prevented engraftment of pancreatic tumor xenografts in murine models and reduced the size of established subcutaneous tumors by at least 3-fold...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28809532/transient-and-local-expression-of-chemokine-and-immune-checkpoint-traps-to-treat-pancreatic-cancer
#16
Lei Miao, Jingjing Li, Qi Liu, Richard Feng, Manisit Das, C Michael Lin, Tyler J Goodwin, Oleksandra Dorosheva, Rihe Liu, Leaf Huang
Pancreatic tumors are known to be resistant to immunotherapy due to the extensive immune suppressive tumor microenvironment (TME). We hypothesized that CXCL12 and PD-L1 are two key molecules controlling the immunosuppressive TME. Fusion proteins, called traps, designed to bind with these two molecules with high affinity (Kd = 4.1 and 0.22 nM, respectively) were manufactured and tested for specific binding with the targets. Plasmid DNA encoding for each trap was formulated in nanoparticles and intravenously injected to mice bearing orthotopic pancreatic cancer...
September 26, 2017: ACS Nano
https://www.readbyqxmd.com/read/28798308/prognostic-value-of-programmed-cell-death-protein-1-expression-on-cd8-t-lymphocytes-in-pancreatic-cancer
#17
Tao Shen, Liangjing Zhou, Hua Shen, Chengfei Shi, Shengnan Jia, Guo Ping Ding, Liping Cao
Pancreatic cancer is one of the most aggressive malignancies and has a highly immunosuppressive tumour microenvironment. Immune checkpoint blockade has led to remarkable and durable objective responses in a number of malignancies and antibody-based strategies targeting programmed cell death protein 1 (PD-1) are showing promise where traditional modalities of surgery, radiotherapy, and chemotherapy have failed. In this study, we examined the clinical value of PD-1 protein expression by CD8+ peripheral T lymphocytes or tumour-infiltrating T lymphocytes (TILs) in pancreatic ductal adenocarcinoma (PDAC)...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28769562/mithramycin-loaded-mpeg-plga-nanoparticles-exert-potent-antitumor-efficacy-against-pancreatic-carcinoma
#18
Xu-Jie Liu, Liang Li, Xiu-Jun Liu, Yi Li, Chun-Yan Zhao, Rui-Qi Wang, Yong-Su Zhen
Previous studies have shown that mithramycin A (MIT) is a promising candidate for the treatment of pancreatic carcinoma through inhibiting transcription factor Sp1. However, systemic toxicities may limit its clinical application. Here, we report a rationally designed formulation of MIT-loaded nanoparticles (MIT-NPs) with a small size and sustained release for improved passive targeting and enhanced therapeutic efficacy. Nearly spherical MIT-NPs with a mean particle size of 25.0±4.6 nm were prepared by encapsulating MIT into methoxy poly(ethylene glycol)-block-poly(d,l-lactic-co-glycolic acid) (mPEG-PLGA) nanoparticles (NPs) with drug loading of 2...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28710747/phase-i-study-of-chimeric-antigen-receptor-modified-t-cells-in-treating-her2-positive-advanced-biliary-tract-cancers-and-pancreatic-cancers
#19
Kaichao Feng, Yang Liu, Yelei Guo, Jingdan Qiu, Zhiqiang Wu, Hanren Dai, Qingming Yang, Yao Wang, Weidong Han
This phase I clinical trial (NCT01935843) is to evaluate the safety, feasibility, and activity of chimeric antigen receptor-engineered T cell (CART) immunotherapy targeting human epidermal growth factor receptor 2 (HER2) in patients with advanced biliary tract cancers (BTCs) and pancreatic cancers (PCs). Eligible patients with HER2-positive (>50%) BTCs and PCs were enrolled in the trial. Well cultured CART-HER2 cells were infused following the conditioning treatment composed of nab-paclitaxel (100-200 mg/m(2)) and cyclophosphamide (15-35 mg/kg)...
July 14, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28710313/ex-vivo-pd-l1-pd-1-pathway-blockade-reverses-dysfunction-of-circulating-cea-specific-t-cells-in-pancreatic-cancer-patients
#20
Yuan Chen, Shao-An Xue, Shahriar Behboudi, Goran H Mohammad, Stephen P Pereira, Emma C Morris
Purpose: Carcinoembryonic antigen (CEA) is a candidate target for cellular immunotherapy of pancreatic cancer. In this study, we have characterized the antigen-specific function of autologous cytotoxic T lymphocytes (CTL) specific for the HLA-A2-restricted peptide, pCEA691-699, isolated from the peripheral T-cell repertoire of pancreatic cancer patients and sought to determine if ex vivo PD-L1 and TIM-3 blockade could enhance CTL function.Experimental Design: CD8(+) T-cell lines were generated from peripheral blood mononuclear cells of 18 HLA-A2(+) patients with pancreatic cancer and from 15 healthy controls...
October 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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