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Nk cells AND pancreatic cancer

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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
#1
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
#2
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
#3
Emma Eriksson, Ioanna Milenova, Jessica Wenthe, Magnus Ståhle, Justyna Leja-Jarblad, Gustav Ullenhag, Anna Dimberg, Rafael 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 activate the CD40 and 4-1BB pathways, respectively...
May 23, 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
#4
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...
May 2, 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
#5
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 Kras(G12D) 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
#6
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...
April 6, 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
#7
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
https://www.readbyqxmd.com/read/28223235/interleukin-32-inflammation-and-cancer
#8
REVIEW
Jin Tae Hong, Dong Ju Son, Chong Kil Lee, Do-Young Yoon, Dong Hun Lee, Mi Hee Park
Interleukin-32 (IL-32) is a novel cytokine involved in inflammation and cancer development. IL-32 gene consists of eight small exons, and IL-32 mRNA has nine alternative spliced isoforms, and was thought to be secreted because it contains an internal signal sequence and lacks a transmembrane region. IL-32 is initially expressed selectively in activated T cells by mitogen and activated NK cells and their expression is strongly augmented by microbes, mitogens, and other cytokines. The IL-32 is induced mainly by pathogens and pro-inflammatory cytokines, but IL-32 is more prominent in immune cells than in non-immune tissues...
February 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28099502/clinical-and-immune-effects-of-lenalidomide-in-combination-with-gemcitabine-in-patients-with-advanced-pancreatic-cancer
#9
RANDOMIZED CONTROLLED TRIAL
Gustav J Ullenhag, Fariba Mozaffari, Mats Broberg, Håkan Mellstedt, Maria Liljefors
PURPOSE: To assess the immunomodulatory and clinical effects of lenalidomide with standard treatment of gemcitabine in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Patients with advanced pancreatic cancer were treated in first line with lenalidomide orally for 21 days of a 28 days cycle and the standard regimen for gemcitabine. In Part I, which we previously have reported, the dose of lenalidomide was defined (n = 12). In Part II, every other consecutive patient was treated with either lenalidomide (Group A, n = 11) or gemcitabine (Group B, n = 10) during cycle 1...
2017: PloS One
https://www.readbyqxmd.com/read/27770341/preoperative-neutrophil-lymphocyte-and-lymphocyte-monocyte-ratios-reflect-immune-cell-population-rearrangement-in-resectable-pancreatic-cancer
#10
Marek Sierzega, Marzena Lenart, Magdalena Rutkowska, Marta Surman, Bozenna Mytar, Andrzej Matyja, Maciej Siedlar, Jan Kulig
BACKGROUND: Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) may serve as a simple index of the immune function. The aim of this study was to investigate the prognostic significance of NLR, PLR, and LMR in patients with resectable pancreatic ductal adenocarcinoma (PDAC) and to verify whether such biomarkers are associated with changes in populations of lymphoid cells. METHODS: The prognostic implications of blood count parameters were evaluated in a retrospective cohort of 442 subjects undergoing pancreatic resections for PDAC...
March 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/27713136/the-role-of-extracellular-vesicles-in-mediating-progression-metastasis-and-potential-treatment-of-hepatocellular-carcinoma
#11
REVIEW
Naibin Yang, Shanshan Li, Guoxiang Li, Shengguo Zhang, Xinyue Tang, Shunlan Ni, Xiaomin Jian, Cunlai Xu, Jiayin Zhu, Mingqin Lu
Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. As vectors for intercellular information exchange, the potential role of extracellular vesicles (EVs) in HCC formation, progression and therapy has been widely investigated. In this review, we explore the current status of the researches in this field. Altogether there is undeniable evidence that EVs play a crucial role in HCC development, metastasis. Moreover, EVs have shown great potential as drug delivery systems (DDSs) for the treatment of HCC...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/27626490/altered-expression-of-cd226-and-cd96-on-natural-killer-cells-in-patients-with-pancreatic-cancer
#12
Yun-Peng Peng, Chun-Hua Xi, Yi Zhu, Ling-Di Yin, Ji-Shu Wei, Jing-Jing Zhang, Xin-Chun Liu, Song Guo, Yue Fu, Yi Miao
The progression of pancreatic cancer (PC) is significantly associated with tumor immune escape, which may be associated with nature killer (NK) cell dysfunction. CD226, CD96, and TIGIT, which share the ligand CD155, play important roles in the regulation of NK cell function. The present study was conducted to investigate the roles of these molecules in NK cells from PC patients. Expression of these molecules on NK cells was detected from samples of 92 pancreatic cancer patients and 40 healthy controls. The expression of CD155 was also evaluated by immunohistochemistry in 88 pancreatic cancer tissues...
October 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27622013/the-proto-oncogene-myc-drives-expression-of-the-nk-cell-activating-nkp30-ligand-b7-h6-in-tumor-cells
#13
Sonja Textor, Felicitas Bossler, Kai-Oliver Henrich, Moritz Gartlgruber, Julia Pollmann, Nathalie Fiegler, Annette Arnold, Frank Westermann, Nina Waldburger, Kai Breuhahn, Sven Golfier, Mathias Witzens-Harig, Adelheid Cerwenka
Natural Killer (NK) cells are innate effector cells that are able to recognize and eliminate tumor cells through engagement of their surface receptors. NKp30 is a potent activating NK cell receptor that elicits efficient NK cell-mediated target cell killing. Recently, B7-H6 was identified as tumor cell surface expressed ligand for NKp30. Enhanced B7-H6 mRNA levels are frequently detected in tumor compared to healthy tissues. To gain insight in the regulation of expression of B7-H6 in tumors, we investigated transcriptional mechanisms driving B7-H6 expression by promoter analyses...
July 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27602753/gemcitabine-inhibits-immune-escape-of-pancreatic-cancer-by-down-regulating-the-soluble-ulbp2-protein
#14
Xiansheng Lin, Mei Huang, Fang Xie, Hangcheng Zhou, Ji Yang, Qiang Huang
Due to early onset of local invasion and distant metastasis, pancreatic cancer is the most lethal human malignant tumor, with a 5 year survival rate of less than 5%. As a effective chemotherapy drug for pancreatic cancer patients, gemcitabine is reported to inhibit cell proliferation as a nucleotide analog. In this study, we investigated the role of gemcitabine in immune regulation of pancreatic cancer. Our data showed that the level of soluble ULBP2 (sULBP2), a ligand of NKG2D receptor, decreased in the supernatants of pancreatic cancer cell lines when gemcitabine was added, and sULBP2 level correlated with NK92 cells cytotoxicity to pancreatic cancer cell lines...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27529227/development-of-a-modular-assay-for-detailed-immunophenotyping-of-peripheral-human-whole-blood-samples-by-multicolor-flow-cytometry
#15
Paul F Rühle, Rainer Fietkau, Udo S Gaipl, Benjamin Frey
The monitoring of immune cells gained great significance in prognosis and prediction of therapy responses. For analyzing blood samples, the multicolor flow cytometry has become the method of choice as it combines high specificity on single cell level with multiple parameters and high throughput. Here, we present a modular assay for the detailed immunophenotyping of blood (DIoB) that was optimized for an easy and direct application in whole blood samples. The DIoB assay characterizes 34 immune cell subsets that circulate the peripheral blood including all major immune cells such as T cells, B cells, natural killer (NK) cells, monocytes, dendritic cells (DCs), neutrophils, eosinophils, and basophils...
August 11, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27471630/evaluation-of-innate-and-adaptive-immunity-contributing-to-the-antitumor-effects-of-pd1-blockade-in-an-orthotopic-murine-model-of-pancreatic-cancer
#16
Marcela D'Alincourt Salazar, Edwin R Manuel, Weimin Tsai, Massimo D'Apuzzo, Leanne Goldstein, Bruce R Blazar, Don J Diamond
Despite the clinical success of anti-PD1 antibody (α-PD1) therapy, the immune mechanisms contributing to the antineoplastic response remain unclear. Here, we describe novel aspects of the immune response involved in α-PD1-induced antitumor effects using an orthotopic Kras (G12D)/p53(R172H)/Pdx1-Cre (KPC) model of pancreatic ductal adenocarcinoma (PDA). We found that positive therapeutic outcome involved both the innate and adaptive arms of the immune system. Adoptive transfer of total splenocytes after short-term (3 d) but not long-term (28 d) PD1 blockade significantly extended survival of non-treated tumor-bearing recipient mice...
June 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27437104/b-cell-regulation-of-the-anti-tumor-response-and-role-in-carcinogenesis
#17
REVIEW
Marc Schwartz, Yu Zhang, Joseph D Rosenblatt
The balance between immune effector cells such as T cells and natural killer cells, and immunosuppressive Treg cells, dendritic, myeloid and monocytic sub-populations in the tumor microenvironment acts to calibrate the immune response to malignant cells. Accumulating evidence is pointing to a role for B cells in modulating the immune response to both solid tumors and hematologic cancer. Evidence from murine autoimmune models has defined B regulatory cell (Breg) subsets that express cytokines such as IL-10, TGF-β, and/or express immune regulatory ligands such as PD-L1, which can suppress T cell and/or natural killer cell responses...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27435400/il-21-enhances-natural-killer-cell-response-to-cetuximab-coated-pancreatic-tumor-cells
#18
Elizabeth L McMichael, Alena Cristina Jaime-Ramirez, Kristan D Guenterberg, Eric Luedke, Lakhvir S Atwal, Amanda R Campbell, Zhiwei Hu, Armika S Tatum, Sri Vidya Kondadasula, Xiaokui Mo, Susheela Tridandapani, Mark Bloomston, E Christopher Ellison, Terence M Williams, Tanios Bekaii-Saab, William E Carson
PURPOSE: Alternative strategies to EGFR blockage by mAbs is necessary to improve the efficacy of therapy in patients with locally advanced or metastatic pancreatic cancer. One such strategy includes the use of NK cells to clear cetuximab-coated tumor cells, as need for novel therapeutic approaches to enhance the efficacy of cetuximab is evident. We show that IL-21 enhances NK cell-mediated effector functions against cetuximab-coated pancreatic tumor cells irrespective of KRAS mutation status...
January 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27297583/blocking-nf-%C3%AE%C2%BAb-is-essential-for-the-immunotherapeutic-effect-of-recombinant-il18-in-pancreatic-cancer
#19
Xingjun Guo, Lei Zheng, Jianxin Jiang, Yan Zhao, Xin Wang, Ming Shen, Feng Zhu, Rui Tian, Chengjian Shi, Meng Xu, Xu Li, Feng Peng, Hang Zhang, Yechen Feng, Yu Xie, Xiaodong Xu, Wei Jia, Ruizhi He, Chencheng Xie, Jun Hu, Dawei Ye, Min Wang, Renyi Qin
PURPOSE: We sought to find new immune-based treatments for pancreatic cancer. EXPERIMENTAL DESIGN: We detected IL18 expression in plasma and specimens from patients with pancreatic cancer. We then investigated whether IL18 had a therapeutic effect for pancreatic cancer in vitro and in vivo and any underlying mechanisms. RESULTS: Higher plasma IL18 was associated with longer overall survival (OS), but higher IL18 in pancreatic cancer tissues was associated with shorter OS and increased invasion and metastasis...
December 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27275582/the-prognostic-impact-of-nk-nkt-cell-density-in-periampullary-adenocarcinoma-differs-by-morphological-type-and-adjuvant-treatment
#20
Sebastian Lundgren, Carl Fredrik Warfvinge, Jacob Elebro, Margareta Heby, Björn Nodin, Agnieszka Krzyzanowska, Anders Bjartell, Karin Leandersson, Jakob Eberhard, Karin Jirström
BACKGROUND: Natural killer (NK) cells and NK T cells (NKT) are vital parts of tumour immunosurveillance. However, their impact on prognosis and chemotherapy response in periampullary adenocarcinoma, including pancreatic cancer, has not yet been described. METHODS: Immune cell-specific expression of CD56, CD3, CD68 and CD1a was analysed by immunohistochemistry on tissue microarrays with tumours from 175 consecutive cases of periampullary adenocarcinoma, 110 of pancreatobiliary type (PB-type) and 65 of intestinal type (I-type) morphology...
2016: PloS One
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