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M2 macrophage + Pancreatic cancer

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https://www.readbyqxmd.com/read/27910859/t-cell-programming-in-pancreatic-adenocarcinoma-a-review
#1
REVIEW
Y D Seo, V G Pillarisetty
Despite recent advancements in multimodal therapy, pancreatic ductal adenocarcinoma (PDA) continues to have a dismal prognosis. In the era of burgeoning immune therapies against previously difficult-to-treat malignancies, there has been growing interest in activating the immune system against PDA; however, unlike in other cancers such as melanoma and lymphoma, immunotherapy has not yielded many clinically significant results. To harness these mechanisms for therapeutic use, an in-depth understanding of T-cell programming in the immune microenvironment of PDA must be achieved...
December 2, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27906162/activation-of-myeloid-and-endothelial-cells-by-cd40l-gene-therapy-supports-t-cell-expansion-and-migration-into-the-tumor-microenvironment
#2
E Eriksson, R Moreno, I Milenova, L Liljenfeldt, L C Dieterich, L Christiansson, H Karlsson, G Ullenhag, S Mangsbo, A Dimberg, R Alemany, A Loskog
CD40 is an interesting target in cancer immunotherapy due to its ability to stimulate Th1 immunity via maturation of dendritic cells and to drive M2 to M1 macrophage differentiation. Pancreatic cancer has a high M2 content that has shown responsive to anti-CD40 agonist therapy and CD40 may thus be a suitable target for immune activation in these patients. In this study, a novel oncolytic adenovirus armed with a trimerized membrane-bound extracellular CD40L (TMZ-CD40L) was evaluated as a treatment of pancreatic cancer...
December 1, 2016: Gene Therapy
https://www.readbyqxmd.com/read/27797715/tumor-associated-macrophage-derived-ccl20-enhances-the-growth-and-metastasis-of-pancreatic-cancer
#3
Bingyan Liu, Yiping Jia, Jun Ma, Shaoqiu Wu, Haosheng Jiang, Yan Cao, Xianjun Sun, Xiang Yin, Shuo Yan, Mingyi Shang, Aiwu Mao
Pancreatic cancer is an aggressive malignancy with a high metastatic potential that results in a high mortality rate worldwide. Although macrophages have the potential to kill tumor cells and elicit immune responses against tumors, there is evidence that tumor-associated macrophages (TAMs) promote tumor progression and suppress T-cell responses. CC-chemokine ligand 20 (CCL20) and its unique receptor CC-chemokine receptor 6 (CCR6) are exploited by cancer cells for migration and metastasis and play important roles in the development and progression of cancer...
October 19, 2016: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/27721235/tumor-associated-macrophages-drive-spheroid-formation-during-early-transcoelomic-metastasis-of-ovarian-cancer
#4
Mingzhu Yin, Xia Li, Shu Tan, Huanjiao Jenny Zhou, Weidong Ji, Stefania Bellone, Xiaocao Xu, Haifeng Zhang, Alessandro D Santin, Ge Lou, Wang Min
Tumor-associated macrophages (TAMs) can influence ovarian cancer growth, migration, and metastasis, but the detailed mechanisms underlying ovarian cancer metastasis remain unclear. Here, we have shown a strong correlation between TAM-associated spheroids and the clinical pathology of ovarian cancer. Further, we have determined that TAMs promote spheroid formation and tumor growth at early stages of transcoelomic metastasis in an established mouse model for epithelial ovarian cancer. M2 macrophage-like TAMs were localized in the center of spheroids and secreted EGF, which upregulated αMβ2 integrin on TAMs and ICAM-1 on tumor cells to promote association between tumor cells and TAM...
November 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27511884/cd14-tlr4-priming-potentially-recalibrates-and-exerts-anti-tumor-efficacy-in-tumor-associated-macrophages-in-a-mouse-model-of-pancreatic-carcinoma
#5
Hridayesh Prakash, Vinod Nadella, Sandhya Singh, Hubertus Schmitz-Winnenthal
Pancreatic cancer is the fourth major cause of cancer related deaths in the world and 5 year survival is below 5%. Among various tumor directed therapies, stimulation of Toll-like receptors (TLR) has shown promising effects in various tumor models. However, pancreatic cancer cells frequently express these receptors themselves and their stimulation (TLR 2 and/or 4 particularly) within tumor microenvironment is known to potentially enhance tumor cell proliferation and cancer progression. Consistent stimulation of tumor associated macrophages (TAMs), in particular with tumor derived TLR ligand within the tumor microenvironment promotes cancer related inflammation, which is sterile, non-immunogenic and carcinogenic in nature...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27471627/mirna-dynamics-in-tumor-infiltrating-myeloid-cells-modulating-tumor-progression-in-pancreatic-cancer
#6
Leonie Mühlberg, Benjamin Kühnemuth, Eithne Costello, Victoria Shaw, Bence Sipos, Magdalena Huber, Heidi Griesmann, Sebastian Krug, Marvin Schober, Thomas M Gress, Patrick Michl
Myeloid cells including tumor-associated macrophages (TAM) and myeloid-derived suppressor cells (MDSC) are known as important mediators of tumor progression in solid tumors such as pancreatic cancer. Infiltrating myeloid cells have been identified not only in invasive tumors, but also in early pre-invasive pancreatic intraepithelial precursor lesions (PanIN). The functional dynamics of myeloid cells during carcinogenesis is largely unknown. We aimed to systematically elucidate phenotypic and transcriptional changes in infiltrating myeloid cells during carcinogenesis and tumor progression in a genetic mouse model of pancreatic cancer...
June 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27454293/rela-a-tale-of-a-stitch-in-time
#7
Murray Korc
Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer in which NF-κB pathways promote biological aggressiveness. In this issue of the JCI, Lesina et al. investigated the role of RelA, the p65 partner of p50 that together form the most common NF-κB complex, in the early stages of pancreatic malignant transformation and in established PDAC. By deleting Rela in the context of an oncogenic Kras-driven autochthonous model of PDAC, the authors demonstrated that RelA is a mediator of oncogene-induced senescence (OIS) and the senescence-associated secretory phenotype (SASP) that attenuates acinar-to-ductal metaplasia, pancreatic intraepithelial neoplasia (PanIN) formation, and PanIN progression to PDAC...
August 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27443257/impact-by-pancreatic-stellate-cells-on-epithelial-mesenchymal-transition-and-pancreatic-cancer-cell-invasion-adding-a-third-dimension-in-vitro
#8
Emelie Karnevi, Ann H Rosendahl, Katarzyna Said Hilmersson, Moin A Saleem, Roland Andersson
Pancreatic cancer is associated with a highly abundant stroma and low-grade inflammation. In the local tumour microenvironment, elevated glucose levels, the presence of tumour-associated stellate cells and macrophages are hypothesised to promote the tumour progression and invasion. The present study investigated the influence by the microenvironment on pancreatic cancer cell invasion in vitro. After co-culture with tumour-associated pancreatic stellate cells (TPSCs), pancreatic cancer cells displayed up to 8-fold reduction in levels of epithelial-mesenchymal transition (EMT) markers E-cadherin and ZO-1, while β-catenin and vimentin levels were increased...
August 15, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27443190/pancreatic-cancer-cell-exosome-mediated-macrophage-reprogramming-and-the-role-of-micrornas-155-and-125b2-transfection-using-nanoparticle-delivery-systems
#9
Mei-Ju Su, Hibah Aldawsari, Mansoor Amiji
Exosomes are nano-sized endosome-derived small intraluminal vesicles, which are important facilitators of intercellular communication by transporting contents, such as protein, mRNA, and microRNAs, between neighboring cells, such as in the tumor microenvironment. The purpose of this study was to understand the mechanisms of exosomes-mediated cellular communication between human pancreatic cancer (Panc-1) cells and macrophages (J771.A1) using a Transwell co-culture system. Following characterization of exosome-mediated cellular communication and pro-tumoral baseline M2 macrophage polarization, the Panc-1 cells were transfected with microRNA-155 (miR-155) and microRNA-125b-2 (miR-125b2) expressing plasmid DNA using hyaluronic acid-poly(ethylene imine)/hyaluronic acid-poly(ethylene glycol) (HA-PEI/HA-PEG) self-assembling nanoparticle-based non-viral vectors...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27271551/immunoglobulin-g4-igg4-positive-plasma-cell-infiltration-is-associated-with-the-clinicopathologic-traits-and-prognosis-of-pancreatic-cancer-after-curative-resection
#10
Qiaofei Liu, Zheyu Niu, Yuan Li, Mengyi Wang, Boju Pan, Zhaohui Lu, Quan Liao, Yupei Zhao
Interactions between pancreatic cancer cells and inflammatory cells play crucial roles in the biological behavior of pancreatic cancer. Abundant infiltration of immunoglobulin G4 (IgG4)-positive plasma cells in the pancreas is the most significant feature of autoimmune pancreatitis; however, the clinical significance of IgG4-positive plasma cell infiltration in pancreatic cancer has not previously been reported. Herein, we analyzed intratumoral and peritumoral infiltrations of IgG4-positive plasma cells in 95 pancreatic cancer cases after curative resection...
August 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/26946344/radiation-therapy-induces-macrophages-to-suppress-t-cell-responses-against-pancreatic-tumors-in-mice
#11
Lena Seifert, Gregor Werba, Shaun Tiwari, Nancy Ngoc Giao Ly, Susanna Nguy, Sara Alothman, Dalia Alqunaibit, Antonina Avanzi, Donnele Daley, Rocky Barilla, Daniel Tippens, Alejandro Torres-Hernandez, Mautin Hundeyin, Vishnu R Mani, Cristina Hajdu, Ilenia Pellicciotta, Philmo Oh, Kevin Du, George Miller
BACKGROUND & AIMS: The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcomes compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive PDAs and accelerates progression of preinvasive foci...
June 2016: Gastroenterology
https://www.readbyqxmd.com/read/26879926/atorvastatin-lipitor-attenuates-the-effects-of-aspirin-on-pancreatic-cancerogenesis-and-the-chemotherapeutic-efficacy-of-gemcitabine-on-pancreatic-cancer-by-promoting-m2-polarized-tumor-associated-macrophages
#12
Qiaofei Liu, Yuan Li, Zheyu Niu, Yi Zong, Mengyi Wang, Lutian Yao, Zhaohui Lu, Quan Liao, Yupei Zhao
BACKGROUND: Interactions of inflammatory cells with pancreatic cancer cells play crucial roles in pancreatic cancer, however the dynamic changes of inflammatory cell populations in pancreatic cancerogensis and after chemotherapy have not been well eclucidated. The combinational use of aspirin and atrovastatin (Lipitor) have been widely prescribled for cardio-cerebral vascular diseases mainly by regulation of inflammations, and they have been also reported to have plausible anti-tumor effects, however their potential roles in pancreatic cancerogenesis and chemotherapeutic effects have been seldom investigated...
2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/26868086/interleukin-27-inhibits-malignant-behaviors-of-pancreatic-cancer-cells-by-targeting-m2-polarized-tumor-associated-macrophages
#13
Lutian Yao, Mengyi Wang, Zheyu Niu, Qiaofei Liu, Xiang Gao, Li Zhou, Quan Liao, Yupei Zhao
Pancreatic cancer is characterized as inflammatory malignancy with a dismal prognosis. There is abundant intratumoral infiltration of macrophages, and most of these tumor associated macrophages (TAM) are induced to be M2 phenotype. The M2 polarized TAM has been demonstrated to promote progression and induce chemo-resistance of pancreatic cancer. Interleukin (IL)-27 is a novel member of IL-12 cytokine family and its roles in regulation of phenotypes and functions of TAM remain largely unknown. In this study, we demonstrated IL-27 significantly inhibited the M2 macrophages polarization and dampened the proliferation, migration and metastasis of pancreatic cancer cells and as well enhanced the efficacy of gemcitabine...
February 8, 2016: Cytokine
https://www.readbyqxmd.com/read/26745602/hdac3-mediates-smoking-induced-pancreatic-cancer
#14
Mouad Edderkaoui, Shiping Xu, Chintan Chheda, Susan Morvaridi, Robert W Hu, Paul J Grippo, Emman Mascariñas, Daniel R Principe, Beatrice Knudsen, Jing Xue, Aida Habtezion, Dale Uyeminami, Kent E Pinkerton, Stephen J Pandol
Smoking is a major risk factor for developing pancreatic adenocarcinoma (PDAC); however, little is known about the mechanisms involved. Here we employed a genetic animal model of early stages of PDAC that overexpresses oncogenic Kras in the pancreas to investigate the mechanisms of smoking-induced promotion of the disease in vivo. We confirmed the regulation of the interactions between the tumor microenvironment cells using in vitro cellular systems. Aerial exposure to cigarette smoke stimulated development of pancreatic intraepithelial neaoplasia (PanIN) lesions associated with a tumor microenvironment-containing features of human PDAC including fibrosis, activated stellate cells, M2-macrophages and markers of epithelial-mesenchymal transition (EMT)...
February 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/26738860/the-m2-phenotype-of-tumor-associated-macrophages-in-the-stroma-confers-a-poor-prognosis-in-pancreatic-cancer
#15
Hai Hu, Jun-Jie Hang, Ting Han, Meng Zhuo, Feng Jiao, Li-Wei Wang
Macrophages play a critical role in the initiation and progression of various solid tumors. However, their prognostic significance in pancreatic ductal adenocarcinoma (PDAC) is poorly understood. This study investigated the distribution patterns of macrophages in PDAC and possible association with the overall survival (OS). We found significant differences in macrophage density (identified by CD68 and CD163 immunopositivity; p < 0.001 for both) between primary cancer and paired adjacent normal tissues...
July 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/26722359/increasing-the-inflammatory-competence-of-macrophages-with-il-6-or-with-combination-of-il-4-and-lps-restrains-the-invasiveness-of-pancreatic-cancer-cells
#16
Aino N E Salmiheimo, Harri K Mustonen, Sanna A A Vainionpää, Zhanlong Shen, Esko A J Kemppainen, Hanna E Seppänen, Pauli A Puolakkainen
Recent studies suggest that pro-inflammatory type M1 macrophages inhibit tumor progression and that anti-inflammatory M2 macrophages enhance it. The aim of this study was to examine the interaction of type M1 and M2 macrophages with pancreatic cancer cells. We studied the migration rate of fluorescein stained pancreatic cancer cells on Matrigel cultured alone or with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) differentiated macrophages or with Macrophage Colony Stimulating Factor (M-CSF) differentiated macrophages, skewing the phenotype towards pro- and anti-inflammatory direction, respectively...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/26641266/metformin-reduces-desmoplasia-in-pancreatic-cancer-by-reprogramming-stellate-cells-and-tumor-associated-macrophages
#17
Joao Incio, Priya Suboj, Shan M Chin, Trupti Vardam-Kaur, Hao Liu, Tai Hato, Suboj Babykutty, Ivy Chen, Vikram Deshpande, Rakesh K Jain, Dai Fukumura
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly desmoplastic tumor with a dismal prognosis for most patients. Fibrosis and inflammation are hallmarks of tumor desmoplasia. We have previously demonstrated that preventing the activation of pancreatic stellate cells (PSCs) and alleviating desmoplasia are beneficial strategies in treating PDAC. Metformin is a widely used glucose-lowering drug. It is also frequently prescribed to diabetic pancreatic cancer patients and has been shown to associate with a better outcome...
2015: PloS One
https://www.readbyqxmd.com/read/26531138/the-pancreatic-cancer-secreted-reg4-promotes-macrophage-polarization-to-m2-through-egfr-akt-creb-pathway
#18
Xiuying Ma, Deqing Wu, Shu Zhou, Feng Wan, Hua Liu, Xiaorong Xu, Xuanfu Xu, Yan Zhao, Maochun Tang
In the periphery of pancreatic ductal adenocarcinoma (PDAC), high accumulation of tumor-associated macrophages (TAMs), which exhibit M2 phenotype, has been shown to be correlated with extra-pancreatic invasion, lymph vessel invasion, lymph node involvement and shortened survival time. However, mechanisms by which tumor cells educate and reprogram TAMs remain largely unclear. The phenotype of TAMs in PDAC tissues was confirmed by immunofluoresence and confocal microscopy. Human CD14+ monocytes were incubated with recombinant human REG4 (rREG4) before being stimulated with LPS and IL-10 and IL-6 were measured with ELISA...
January 2016: Oncology Reports
https://www.readbyqxmd.com/read/26166469/characterization-of-mouse-models-of-early-pancreatic-lesions-induced-by-alcohol-and-chronic-pancreatitis
#19
COMPARATIVE STUDY
Shiping Xu, Chintan Chheda, Yassine Ouhaddi, Hajar Benhaddou, Mouloud Bourhim, Paul J Grippo, Daniel R Principe, Emman Mascariñas, Brian DeCant, Hidekazu Tsukamoto, Stephen J Pandol, Mouad Edderkaoui
OBJECTIVE: We describe the first mouse model of pancreatic intraepithelial neoplasia (PanIN) lesions induced by alcohol in the presence and absence of chronic pancreatitis. METHODS: Pdx1-Cre;LSL-K-ras mice were exposed to Lieber-DeCarli alcohol diet for 6 weeks with cerulein injections. The PanIN lesions and markers of fibrosis, inflammation, histone deacetylation, epithelial-to-mesenchymal transition (EMT), and cancer stemness were measured by immunohistochemistry and Western...
August 2015: Pancreas
https://www.readbyqxmd.com/read/25827621/inflammatory-features-of-pancreatic-cancer-highlighted-by-monocytes-macrophages-and-cd4-t-cells-with-clinical-impact
#20
Takuya Komura, Yoshio Sakai, Kenichi Harada, Kazunori Kawaguchi, Hisashi Takabatake, Hirohisa Kitagawa, Takashi Wada, Masao Honda, Tetsuo Ohta, Yasuni Nakanuma, Shuichi Kaneko
Pancreatic ductal adenocarcinoma (PDAC) is among the most fatal of malignancies with an extremely poor prognosis. The objectives of this study were to provide a detailed understanding of PDAC pathophysiology in view of the host immune response. We examined the PDAC tissues, sera, and peripheral blood cells of PDAC patients using immunohistochemical staining, the measurement of cytokine/chemokine concentrations, gene expression analysis, and flow cytometry. The PDAC tissues were infiltrated by macrophages, especially CD33+CD163+ M2 macrophages and CD4+ T cells that concomitantly express programmed cell death-1 (PD-1)...
June 2015: Cancer Science
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