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Nk cells AND pancreatic cancer

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https://www.readbyqxmd.com/read/29725336/tribody-her2-2-xcd16-is-more-effective-than-trastuzumab-in-enhancing-%C3%AE-%C3%AE-t-cell-and-natural-killer-cell-cytotoxicity-against-her2-expressing-cancer-cells
#1
Hans H Oberg, Christian Kellner, Daniel Gonnermann, Susanne Sebens, Dirk Bauerschlag, Martin Gramatzki, Dieter Kabelitz, Matthias Peipp, Daniela Wesch
An enhanced expression of human epidermal growth factor receptor 2 (HER2, ErbB2) often occurs in an advanced stage of breast, ovarian, gastric or esophageal cancer, and pancreatic ductal adenocarcinoma (PDAC). Commonly, HER2 expression is associated with poor clinical outcome or chemoresistance in ovarian and breast cancer patients. Treatment with humanized anti-HER2 monoclonal antibodies, such as trastuzumab or pertuzumab, has improved the outcome of patients with HER2-positive metastatic gastric or breast cancer, but not all patients benefit...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29721386/in-situ-delivery-of-allogeneic-natural-killer-cell-nk-combined-with-cetuximab-in-liver-metastases-of-gastrointestinal-carcinoma-a-phase-i-clinical-trial
#2
O Adotevi, Y Godet, J Galaine, Z Lakkis, I Idirene, J M Certoux, M Jary, R Loyon, C Laheurte, S Kim, A Dormoy, F Pouthier, C Barisien, F Fein, P Tiberghien, X Pivot, S Valmary-Degano, C Ferrand, P Morel, E Delabrousse, C Borg
Despite successful introduction of NK-based cellular therapy in the treatment of myeloid leukemia, the potential use of NK alloreactivity in solid malignancies is still elusive. We performed a phase I clinical trial to assess the safety and efficacy of in situ delivery of allogeneic NK cells combined with cetuximab in liver metastasis of gastrointestinal origin. The conditioning chemotherapy was administrated before the allogeneic NK cells injection via hepatic artery. Three escalating doses were tested (3...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29660367/natural-killer-cells-and-their-therapeutic-role-in-pancreatic-cancer-a-systematic-review
#3
REVIEW
Jonas R M Van Audenaerde, Geert Roeyen, Phillip K Darcy, Michael H Kershaw, M Peeters, Evelien L J Smits
Pancreatic cancer is among the three deadliest cancers worldwide with the lowest 5-year survival of all cancers. Despite all efforts, therapeutic improvements have barely been made over the last decade. Even recent highly promising targeted and immunotherapeutic approaches did not live up to their expectations. Therefore, other horizons have to be explored. Natural Killer (NK) cells are gaining more and more interest as a highly attractive target for cancer immunotherapies, both as pharmaceutical target and for cell therapies...
April 13, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29515971/the-expression-and-prognostic-impact-of-immune-cytolytic-activity-related-markers-in-human-malignancies-a-comprehensive-meta-analysis
#4
Constantinos Roufas, Dimitrios Chasiotis, Anestis Makris, Christodoulos Efstathiades, Christos Dimopoulos, Apostolos Zaravinos
Background: Recently, immune-checkpoint blockade has shown striking clinical results in different cancer patients. However, a significant inter-individual and inter-tumor variability exists among different cancers. The expression of the toxins granzyme A (GZMA) and perforin 1 (PRF1), secreted by effector cytotoxic T cells and natural killer (NK) cells, were recently used as a denominator of the intratumoral immune cytolytic activity (CYT). These levels are significantly elevated upon CD8+ T-cell activation as well as during a productive clinical response against immune-checkpoint blockade therapies...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29363526/nitric-oxide-production-by-myeloid-derived-suppressor-cells-plays-a-role-in-impairing-fc-receptor-mediated-natural-killer-cell-function
#5
Andrew Stiff, Prashant Trikha, Bethany Mundy-Bosse, Elizabeth McMichael, Thomas A Mace, Brooke Benner, Kari Kendra, Amanda Campbell, Shalini Gautam, David Abood, Ian Landi, Vincent Hsu, Megan Duggan, Robert Wesolowski, Matthew Old, John Harrison Howard, Lianbo Yu, Nancy Stasik, Thomas Olencki, Natarajan Muthusamy, Susheela Tridandapani, John C Byrd, Michael Caligiuri, William E Carson
Purpose: mAbs are used to treat solid and hematologic malignancies and work in part through Fc receptors (FcRs) on natural killer cells (NK). However, FcR-mediated functions of NK cells from patients with cancer are significantly impaired. Identifying the mechanisms of this dysfunction and impaired response to mAb therapy could lead to combination therapies and enhance mAb therapy. Experimental Design: Cocultures of autologous NK cells and MDSC from patients with cancer were used to study the effect of myeloid-derived suppressor cells (MDSCs) on NK-cell FcR-mediated functions including antibody-dependent cellular cytotoxicity, cytokine production, and signal transduction in vitro Mouse breast cancer models were utilized to study the effect of MDSCs on antibody therapy in vivo and test the efficacy of combination therapies including a mAb and an MDSC-targeting agent...
April 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29203590/a-first-in-human-phase-i-study-of-subcutaneous-outpatient-recombinant-human-il15-rhil15-in-adults-with-advanced-solid-tumors
#6
Jeffrey S Miller, Chihiro Morishima, Douglas G McNeel, Manish R Patel, Holbrook E K Kohrt, John A Thompson, Paul M Sondel, Heather A Wakelee, Mary L Disis, Judith C Kaiser, Martin A Cheever, Howard Streicher, Steven P Creekmore, Thomas A Waldmann, Kevin C Conlon
Purpose: Preclinical data established IL15 as a homeostatic factor and powerful stimulator of NK and CD8+ T-cell function, the basis for clinical testing. Experimental Design: A first-in-human outpatient phase I dose escalation trial of subcutaneous (SC) rhIL15 was conducted in refractory solid tumor cancer patients. Therapy consisted of daily (Monday-Friday) subcutaneous injections of rhIL15 for two consecutive weeks (10 total doses/cycle). Clinical response was assessed by RECIST. Pharmacokinetics of rhIL15 and immune biomarkers were evaluated...
December 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29180478/perioperative-spatiotemporally-coordinated-activation-of-t-and-nk-cells-prevents-recurrence-of-pancreatic-cancer
#7
Jennifer Brooks, Bettina Fleischmann-Mundt, Norman Woller, Julia Niemann, Silvia Ribback, Kristin Peters, Ihsan Ekin Demir, Nina Armbrecht, Guralp O Ceyhan, Michael P Manns, Thomas C Wirth, Stefan Kubicka, Gunter Bernhardt, Mark J Smyth, Diego F Calvisi, Engin Gürlevik, Florian Kühnel
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal and disseminating cancer resistant to therapy, including checkpoint immunotherapies, and early tumor resection and (neo)adjuvant chemotherapy fails to improve a poor prognosis. In a transgenic mouse model of resectable PDAC, we investigated the coordinated activation of T and natural killier (NK) cells in addition to gemcitabine chemotherapy to prevent tumor recurrence. Only neoadjuvant, but not adjuvant treatment with a PD-1 antagonist effectively supported chemotherapy and suppressed local tumor recurrence and improved survival involving both NK and T cells...
January 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/28967637/anti-cancer-efficiency-of-natural-killer-cells-differentiated-from-human-adipose-tissue-derived-mesenchymal-stem-cells-and-transfected-with-mirna150
#8
A Karlitepe, H Kabadayi, S Vatansever, M Gurdal, C Gunduz, G Ercan
AIM: The aim of this study is to investigate the effects of miR150 transfection on NK-like cells differentiated from adipose tissue derived mesenchymal stem cells (AD-MSCs). METHODS: NK-like cells were differentiated from AD-MSCs and activated by miR150 transfection. Transfected/non-transfected NK-like cells were characterized by immunohistochemical and RT-PCR analyzes. Apoptotic efficiency of the transfected/non-transfected NK-like cells on pancreatic cancer cells PANC1 were determined by TUNEL and RT-PCR...
September 2017: Experimental Oncology
https://www.readbyqxmd.com/read/28928888/potential-roles-of-peripheral-dopamine-in-tumor-immunity
#9
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/28915646/interleukin-15-stimulates-natural-killer-cell-mediated-killing-of-both-human-pancreatic-cancer-and-stellate-cells
#10
Jonas R M Van Audenaerde, Jorrit De Waele, Elly Marcq, Jinthe Van Loenhout, Eva Lion, Johan M J Van den Bergh, Ralf Jesenofsky, Atsushi Masamune, Geert Roeyen, Patrick Pauwels, Filip Lardon, Marc Peeters, Evelien L J Smits
Pancreatic ductal adenocarcinoma (PDAC) is the 4(th) leading cause of cancer-related death in Western countries with a 5-year survival rate below 5%. One of the hallmarks of this cancer is the strong desmoplastic reaction within the tumor microenvironment (TME), orchestrated by activated pancreatic stellate cells (PSC). This results in a functional and mechanical shield which causes resistance to conventional therapies. Aiming to overcome this resistance by tackling the stromal shield, we assessed for the first time the capacity of IL-15 stimulated natural killer (NK) cells to kill PSC and pancreatic cancer cells (PCC)...
August 22, 2017: Oncotarget
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
#11
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)...
December 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28870891/lidocaine-stimulates-the-function-of-natural-killer-cells-in-different-experimental-settings
#12
REVIEW
Juan P Cata, Maria F Ramirez, Jose F Velasquez, A I Di, Keyuri U Popat, Vijaya Gottumukkala, Dahlia M Black, Valerae O Lewis, Jean N Vauthey
BACKGROUND: One of the functions of natural killer (NK) cells is to eliminate cancer cells. The cytolytic activity of NK cells is tightly regulated by inhibitory and activation receptors located in the surface membrane. Lidocaine stimulates the function of NK cells at clinically relevant concentrations. It remains unknown whether this effect of lidocaine has an impact on the expression of surface receptors of NK cells, can uniformly stimulate across different cancer cell lines, and enhances the function of cells obtained during oncological surgery...
September 2017: Anticancer Research
https://www.readbyqxmd.com/read/28857157/newcastle-disease-virus-mediates-pancreatic-tumor-rejection-via-nk-cell-activation-and-prevents-cancer-relapse-by-prompting-adaptive-immunity
#13
Theresa Schwaiger, Michael R Knittler, Christian Grund, Angela Roemer-Oberdoerfer, Joachim-Friedrich Kapp, Markus M Lerch, Thomas C Mettenleiter, Julia Mayerle, Ulrike Blohm
Pancreatic cancer is the 8th most common cause of cancer-related deaths worldwide and the tumor with the poorest prognosis of all solid malignancies. In 1957, it was discovered that Newcastle disease virus (NDV) has oncolytic properties on tumor cells. To study the oncolytic properties of NDV in pancreatic cancer a single dose was administered intravenously in a syngeneic orthotopic tumor model using two different murine pancreatic adenocarcinoma cell lines (DT6606PDA, Panc02). Tumor growth was monitored and immune response was analyzed...
December 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28714337/correlation-between-natural-killer-cell-activity-and-systemic-inflammatory-markers-for-heterogeneous-cancer-patients-treated-with-wheel-balance-cancer-therapy
#14
Hwi-Joong Kang, Kyeore Bae, Jee-Hye Kim, Chong-Kwan Cho, Hwa-Seung Yoo
BACKGROUND AND OBJECTIVE: Natural killer (NK) cells are known to have an effect on the prevention of tumorigenesis for the initial cancer, as well as the metastatic cancer. For the past several years, the relationship between cancer and inflammation has been actively studied in preclinical and clinical settings, but there are no reports on alterations in and correlation for NK cell activity (NKA) and systemic inflammatory markers. Accordingly, this study aimed to measure correlation between NKA and the levels of other systemic inflammatory markers in patients with gastric, breast, and pancreatic cancer who received Wheel Balance Cancer Therapy (WBCT)...
July 1, 2017: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/28615524/interleukin-15-stimulates-natural-killer-cell-mediated-killing-of-both-human-pancreatic-cancer-and-stellate-cells
#15
Jonas R M Van Audenaerde, Jorrit De Waele, Elly Marcq, Jinthe Van Loenhout, Eva Lion, Johan M J Van den Bergh, Ralf Jesenofsky, Atsushi Masamune, Geert Roeyen, Patrick Pauwels, Filip Lardon, Marc Peeters, Evelien L J Smits
Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer-related death in Western countries with a 5-year survival rate below 5%. One of the hallmarks of this cancer is the strong desmoplastic reaction within the tumor microenvironment (TME), orchestrated by activated pancreatic stellate cells (PSC). This results in a functional and mechanical shield which causes resistance to conventional therapies. Aiming to overcome this resistance by tackling the stromal shield, we assessed for the first time the capacity of IL-15 stimulated natural killer (NK) cells to kill PSC and pancreatic cancer cells (PCC)...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28536305/shaping-the-tumor-stroma-and-sparking-immune-activation-by-cd40-and-4-1bb-signaling-induced-by-an-armed-oncolytic-virus
#16
Emma Eriksson, Ioanna Milenova, Jessica Wenthe, Magnus Ståhle, Justyna Leja-Jarblad, Gustav Ullenhag, Anna Dimberg, Raphael Moreno, Ramon Alemany, Angelica Loskog
Purpose: Pancreatic cancer is a severe indication with short expected survival despite surgery and/or combination chemotherapeutics. Checkpoint blockade antibodies are approved for several cancer indications, but pancreatic cancer has remained refractory. However, there are clinical data suggesting that stimulation of the CD40 pathway may be of interest for these patients. Oncolytic viruses armed with immunostimulatory genes represent an interesting approach. Herein, we present LOAd703, a designed adenovirus armed with trimerized CD40L and 4-1BBL that activates the CD40 and 4-1BB pathways, respectively...
October 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28465448/elevated-interferon-%C3%AE-induced-protein-10-and-its-receptor-cxcr3-impair-nk-cell-function-during-hiv-infection
#17
Zhuo Wang, Tong Wu, Meichen Ma, Zining Zhang, Yajing Fu, Jing Liu, Junjie Xu, Haibo Ding, Xiaoxu Han, Zhenxing Chu, Yuntao Wu, Hong Shang, Yongjun Jiang
As the first line of defense in the human immune system, NK cells play essential roles in prevention of tumorigenesis and viral infection. It is known that NK cells have impaired function in HIV infection; however, it remains unclear why this occurs. IP-10 is a chemokine and inflammatory factor that is associated with such diseases as tuberculosis, hepatitis B virus, and pancreatic cancer. The aim of this study was to evaluate IP-10 levels and CXCR3 expression in NK cells that were affected by HIV and to elucidate whether NK cell function could be affected by IP-10...
July 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28419443/loss-of-natural-killer-t-cells-promotes-pancreatic-cancer-in-lsl-kras-g12d-mice
#18
Naveena B Janakiram, Altaf Mohammed, Taylor Bryant, Rebekah Ritchie, Nicole Stratton, Lydgia Jackson, Stan Lightfoot, Doris M Benbrook, Adam S Asch, Mark L Lang, Chinthalapally V Rao
The role of the unique T-cell population, natural killer T (NKT) cells, which have similar functions to NK cells in pancreatic cancer (PC), is not yet evaluated. To address the regulatory roles of NKT cells on tumour progression through tumour-associated macrophages (TAM) and their production of microsomal prostaglandin E synthase-1 (mPGES-1) and 5-lipoxygenase (5-LOX) in (Kras)-driven pancreatic tumour (KPT) progression, we crossed CD1d-/- mice deficient in both invariant and variant NKT cells with the KrasG12D mice...
September 2017: Immunology
https://www.readbyqxmd.com/read/28392199/short-term-clinical-efficacy-of-percutaneous-irreversible-electroporation-combined-with-allogeneic-natural-killer-cell-for-treating-metastatic-pancreatic-cancer
#19
Mao Lin, Shuzhen Liang, Xiaohua Wang, Yinqing Liang, Mingjie Zhang, Jibing Chen, Lizhi Niu, Kecheng Xu
This study was to determine how the short-term clinical efficacy of irreversible electroporation (IRE) combined with allogeneic natural killer (NK) cell therapy for treating metastatic pancreatic cancer. Between March and December 2016, we enrolled 40 patients who met the enrollment criteria and assigned them to two groups: simple IRE (IRE group, n=20) and IRE plus allogeneic NK cell therapy (IRE-NK, n=20). We evaluated immune function changes, quality of life, clinical response, and other related indicators...
June 2017: Immunology Letters
https://www.readbyqxmd.com/read/28367234/differentiation-by-nk-cells-is-a-prerequisite-for-effective-targeting-of-cancer-stem-cells-poorly-differentiated-tumors-by-chemopreventive-and-chemotherapeutic-drugs
#20
Anna Karolina Kozlowska, Paytsar Topchyan, Kawaljit Kaur, Han-Ching Tseng, Antonia Teruel, Toru Hiraga, Anahid Jewett
Natural Killer (NK) cells target oral, pancreatic, lung, breast, glioblastoma and melanoma stem-like/poorly differentiated tumors. Differentiation of the abovementioned tumors with supernatants from split-anergized NK cells decreases their susceptibility to NK cells, but increases their sensitivity to cisplatin (CDDP)-mediated cell death. Breast and melanoma tumor cells with CD44 knockdown display enhanced susceptibility to NK cell-mediated lysis, potentially due to decreased differentiation. We also demonstrate that sulindac, a non-steroidal anti-inflammatory drug and a chemopreventive agent, not only limits the growth of oral tumor cells, but also aids in cancer cell elimination by NK cells...
2017: Journal of Cancer
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