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M2 macrophage + Pancreatic cancer

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https://www.readbyqxmd.com/read/29066497/t-cell-localization-activation-and-clonal-expansion-in-human-pancreatic-ductal-adenocarcinoma
#1
Ingunn M Stromnes, Ayaka Hulbert, Robert H Pierce, Philip D Greenberg, Sunil R Hingorani
Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy resistant to most therapies, including immune checkpoint blockade. To elucidate mechanisms of immunotherapy resistance, we assessed immune parameters in resected human PDA. We demonstrate significant interpatient variability in T-cell number, localization, and phenotype. CD8(+) T cells, Foxp3(+) regulatory T cells, and PD-1(+) and PD-L1(+) cells were preferentially enriched in tertiary lymphoid structures that were found in most tumors compared with stroma and tumor cell nests...
November 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28957348/-stealth-dissemination-of-macrophage-tumor-cell-fusions-cultured-from-blood-of-patients-with-pancreatic-ductal-adenocarcinoma
#2
Gary A Clawson, Gail L Matters, Ping Xin, Christopher McGovern, Eric Wafula, Claude dePamphilis, Morgan Meckley, Joyce Wong, Luke Stewart, Christopher D'Jamoos, Naomi Altman, Yuka Imamura Kawasawa, Zhen Du, Loren Honaas, Thomas Abraham
Here we describe isolation and characterization of macrophage-tumor cell fusions (MTFs) from the blood of pancreatic ductal adenocarcinoma (PDAC) patients. The MTFs were generally aneuploidy, and immunophenotypic characterizations showed that the MTFs express markers characteristic of PDAC and stem cells, as well as M2-polarized macrophages. Single cell RNASeq analyses showed that the MTFs express many transcripts implicated in cancer progression, LINE1 retrotransposons, and very high levels of several long non-coding transcripts involved in metastasis (such as MALAT1)...
2017: PloS One
https://www.readbyqxmd.com/read/28750018/pancreatic-cancer-cell-fibroblast-co-culture-induces-m2-like-macrophages-that-influence-therapeutic-response-in-a-3d-model
#3
Janina Kuen, Diana Darowski, Tobias Kluge, Meher Majety
Pancreatic cancer (PC) remains one of the most challenging solid tumors to treat with a high unmet medical need as patients poorly respond to standard-of-care-therapies. Prominent desmoplastic reaction involving cancer-associated fibroblasts (CAFs) and the immune cells in the tumor microenvironment (TME) and their cross-talk play a significant role in tumor immune escape and progression. To identify the key cellular mechanisms induce an immunosuppressive tumor microenvironment, we established 3D co-culture model with pancreatic cancer cells, CAFs and monocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28749946/genome-wide-association-analysis-identifies-genetic-correlates-of-immune-infiltrates-in-solid-tumors
#4
Nathan O Siemers, James L Holloway, Han Chang, Scott D Chasalow, Petra B Ross-MacDonald, Charles F Voliva, Joseph D Szustakowski
Therapeutic options for the treatment of an increasing variety of cancers have been expanded by the introduction of a new class of drugs, commonly referred to as checkpoint blocking agents, that target the host immune system to positively modulate anti-tumor immune response. Although efficacy of these agents has been linked to a pre-existing level of tumor immune infiltrate, it remains unclear why some patients exhibit deep and durable responses to these agents while others do not benefit. To examine the influence of tumor genetics on tumor immune state, we interrogated the relationship between somatic mutation and copy number alteration with infiltration levels of 7 immune cell types across 40 tumor cohorts in The Cancer Genome Atlas...
2017: PloS One
https://www.readbyqxmd.com/read/28476581/tumour-associated-macrophages-activate-migration-and-stat3-in-pancreatic-ductal-adenocarcinoma-cells-in-co-cultures
#5
Aino Salmiheimo, Harri Mustonen, Sanna Vainionpää, Zhanlong Shen, Esko Kemppainen, Pauli Puolakkainen, Hanna Seppänen
OBJECTIVES: Tumour-associated macrophages participate in tumour development and progression. The aim of this study was to assess the interactions of pancreatic cancer cells and pro-inflammatory M1 and anti-inflammatory M2 macrophages, specifically their effect on pancreatic cancer cell migration and the changes in STAT-signalling. METHODS: Monocytes were isolated from healthy subjects and differentiated into macrophages with M-CSF. The macrophages were polarized towards M1 by IL-12 and towards M2 by IL-10...
July 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28419443/loss-of-natural-killer-t-cells-promotes-pancreatic-cancer-in-lsl-kras-g12d-mice
#6
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/28348045/stratification-of-pancreatic-ductal-adenocarcinoma-combinatorial-genetic-stromal-and-immunologic-markers
#7
Erik S Knudsen, Paris Vail, Uthra Balaji, Hoai Ngo, Ihab W Botros, Vladimir Makarov, Nadeem Riaz, Vinod Balachandran, Steven Leach, Debrah M Thompson, Timothy A Chan, Agnieszka K Witkiewicz
Purpose: Pancreatic ductal adenocarcinoma (PDAC) is associated with an immunosuppressive milieu that supports immune system evasion and disease progression. Here, we interrogated genetic, stromal, and immunologic features of PDAC to delineate impact on prognosis and means to more effectively employ immunotherapy.Experimental Design: A cohort of 109 PDAC cases annotated for overall survival was utilized as a primary discovery cohort. Gene expression analysis defined immunologic subtypes of PDAC that were confirmed in the Cancer Genome Atlas dataset...
March 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28124184/reelin-deficiency-delays-mammary-tumor-growth-and-metastatic-progression
#8
Elvira Khialeeva, Joan W Chou, Denise E Allen, Alec M Chiu, Steven J Bensinger, Ellen M Carpenter
Reelin is a regulator of cell migration in the nervous system, and has other functions in the development of a number of non-neuronal tissues. In addition, alterations in reelin expression levels have been reported in breast, pancreatic, liver, gastric, and other cancers. Reelin is normally expressed in mammary gland stromal cells, but whether stromal reelin contributes to breast cancer progression is unknown. Herein, we used a syngeneic mouse mammary tumor transplantation model to examine the impact of host-derived reelin on breast cancer progression...
March 2017: Journal of Mammary Gland Biology and Neoplasia
https://www.readbyqxmd.com/read/28108630/macropinocytosis-of-nab-paclitaxel-drives-macrophage-activation-in-pancreatic-cancer
#9
Jane Cullis, Despina Siolas, Antonina Avanzi, Sugata Barui, Anirban Maitra, Dafna Bar-Sagi
Pancreatic cancer is a devastating disease that is largely refractory to currently available treatment strategies. Therapeutic resistance is partially attributed to the dense stromal reaction of pancreatic ductal adenocarcinoma tumors that includes a pervasive infiltration of immunosuppressive (M2) macrophages. Nab-paclitaxel (trade name Abraxane) is a nanoparticle albumin-bound formulation of paclitaxel that, in combination with gemcitabine, is currently the first-line treatment for pancreatic cancer. Here, we show that macrophages internalized nab-paclitaxel via macropinocytosis...
March 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28097809/cancer-associated-fibroblasts-promote-m2-polarization-of-macrophages-in-pancreatic-ductal-adenocarcinoma
#10
Aibin Zhang, Yigang Qian, Zhou Ye, Haiyong Chen, Haiyang Xie, Lin Zhou, Yan Shen, Shusen Zheng
Pancreatic ductal adenocarcinoma (PDAC) is characterized by remarkable desmoplasia with infiltration of distinct cellular components. Cancer-associated fibroblasts (CAFs) has been shown to be among the most prominent cells and played a significant role in shaping the tumor microenvironment by interacting with other type of cells. Here, we aimed to investigate the effect of CAFs in modulating phenotype of tumor-associated macrophages (TAM). Under treatment of CAFs conditioned medium (CM) or direct co-culture with CAFs, monocytes exhibited enhanced expression of CD206 and CD163 compared with control group (P < 0...
February 2017: Cancer Medicine
https://www.readbyqxmd.com/read/27910859/t-cell-programming-in-pancreatic-adenocarcinoma-a-review
#11
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...
March 2017: 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
#12
E Eriksson, R Moreno, I Milenova, L Liljenfeldt, L C Dieterich, L Christiansson, H Karlsson, G Ullenhag, S M Mangsbo, A Dimberg, R Alemany, A Loskog
CD40 is an interesting target in cancer immunotherapy due to its ability to stimulate T-helper 1 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...
February 2017: Gene Therapy
https://www.readbyqxmd.com/read/27797715/tumor-associated-macrophage-derived-ccl20-enhances-the-growth-and-metastasis-of-pancreatic-cancer
#13
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...
December 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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