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tumor associated macrophages

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https://www.readbyqxmd.com/read/28526770/therapeutic-ige-antibodies-harnessing-a-macrophage-mediated-immune-surveillance-mechanism-against-cancer
#1
REVIEW
Sophia N Karagiannis, Debra H Josephs, Heather J Bax, James F Spicer
IgG monoclonal antibodies have made significant contributions to cancer therapy, but suffer from several limitations that restrict their effectiveness in unleashing host immune system components against tumors. The development of monoclonal antibodies of an alternative class, namely IgE, may offer enhanced immune surveillance and superior effector cell potency against cancer cells. In our recent article, we elaborate our proof-of-concept studies of a mouse/human chimeric IgE antibody (MOv18 IgE), which is specific for the cancer-associated antigen folate receptor alpha...
May 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28524544/enzymatic-engineering-of-live-bacterial-cell-surface-using-butelase-1
#2
Xiaobao Bi, Juan Yin, Giang K T Nguyen, Chang Rao, Nurashikin Bte Abdul Halim, Xinya Hemu, James P Tam, Chuan-Fa Liu
We show that butelase-mediated ligation (BML) can be used to modify live bacterial cell surfaces with diverse cargo molecules. Surface-displayed butelase recognition motif NHV was first introduced at the C-terminal end of the anchoring protein OmpA on E. coli cells. This then served as a handle of BML for the functionalization of E. coli cell surfaces with fluorescein and biotin tags, a tumor-associated monoglycosylated peptide and mCherry protein. The cell-surface ligation reaction was achieved at low concentrations of butelase and the labeling substrates...
May 19, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28522599/engineering-macrophages-to-eat-cancer-from-marker-of-self-cd47-and-phagocytosis-to-differentiation
#3
REVIEW
Cory Alvey, Dennis E Discher
The ability of a macrophage to engulf and break down invading cells and other targets provides a first line of immune defense in nearly all tissues. This defining ability to "phagos" or devour can subsequently activate the entire immune system against foreign and diseased cells, and progress is now being made on a decades-old idea of directing macrophages to phagocytose specific targets, such as cancer cells. Engineered T cells provide precedence with recent clinical successes against liquid tumors, but solid tumors remain a challenge, and a handful of clinical trials seek to exploit the abundance of tumor-associated macrophages instead...
May 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28522566/nedd8-modification-of-cullin-5-regulates-lipopolysaccharide-induced-acute-lung-injury
#4
Ziyan Zhu, Lei Sun, Rui Hao, Hongchao Jiang, Feng Qian, Richard D Ye
Lung infections are major causes of acute lung injury (ALI), with limited effective treatment available. Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an essential adaptor regulating Toll-like receptors (TLRs). We recently identified Cullin-5 (Cul-5) as a prominent component in the regulation of TRAF6 polyubiquitination, but its physiological significance in acute lung injury has not been explored. In this study, we investigated the potential role of Cul-5 in regulating ALI using mice receiving intratracheal instillation of LPS...
May 18, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28521292/tumor-infiltrating-immune-cells-and-prognosis-in-gastric-cancer-a-systematic-review-and-meta-analysis
#5
Wen Jiang, Ke Liu, Qing Guo, Ji Cheng, Liming Shen, Yinghao Cao, Jing Wu, Jianguo Shi, Heng Cao, Bo Liu, Kaixiong Tao, Guobin Wang, Kailin Cai
Tumor-infiltrating immune cells are a pivotal component of the tumor microenvironment (TME), but their indicative role remains poorly defined. A meta-analysis was performed to reveal the prognostic efficiency of tumor-infiltrating immune cells in gastric cancer (GC). By searching PubMed and Embase, we identified a total of 35 eligible articles that involved 4888 patients. Random or fixed effect models were employed to extract pooled hazard ratios (HRs) with 95% confidence intervals (CIs). Our results indicated that high CD3+ lymphocyte infiltration in all the locations (AG), the tumor nest (TN), and the tumor stroma (TS) predicted better overall survival (OS) (HR=0...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28515351/local-immune-response-depends-on-p16ink4a-status-of-primary-tumor-in-vulvar-squamous-cell-carcinoma
#6
Jacek J Sznurkowski, Anton Żawrocki, Wojciech Biernat
BACKGROUND: The p16Ink4a is not a surrogate marker for high-risk human papilloma virus (HPV) genotypes but indicates better prognosis in vulvar squamous cell carcinoma patients. Our recent study confirmed substantial mismatch between p16Ink4a and high-risk HPV-status as well as revealed that p16Ink4a-overexpression itself is an independent prognostic factor for vulvar cancer. AIM: To determine significance of the tumor infiltrating immune cells and p16Ink4a-status for better outcome of patients with vulvar cancer...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28515123/all-trans-retinoic-acid-prevents-osteosarcoma-metastasis-by-inhibiting-m2-polarization-of-tumor-associated-macrophages
#7
Qian Zhou, Miao Xian, Senfeng Xiang, Danyan Xiang, Xuejing Shao, Jincheng Wang, Ji Cao, Xiaochun Yang, Bo Yang, Meidan Ying, Qiaojun He
M2-polarized tumor associated macrophages (TAM) play a critical role in cancer invasion and metastasis. Here, we report that M2 macrophages enhanced metastasis of K7M2 WT osteosarcoma cells to the lung in mice, thus establishing M2 TAMs as a therapeutic target for blocking osteosarcoma metastasis. We found that all-trans retinoic acid (ATRA) inhibited osteosarcoma metastasis via inhibiting the M2 polarization of TAMs. ATRA suppressed IL13 or IL4 induced M2-type macrophages, and then inhibited migration of osteosarcoma cells as promoted by M2-type macrophages in vitro ATRA reduced the number of pulmonary metastatic nodes of osteosarcoma and decreased expression of M2-type macrophages in metastatic nodes both in intravenous injection and orthotopic transplantation models...
May 17, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28512410/rrx-001-priming-of-pd-1-inhibition-in-the-treatment-of-small-cell-carcinoma-of-the-vagina-a-rare-gynecological-tumor
#8
Christina Brzezniak, Bryan Oronsky, Jane Trepel, Thomas A Summers, Pedro Cabrales, Min-Jung Lee, Regina Day, Saheli Jha, Scott Caroen, Karen Zeman, Lindsey Ferry, Cindy Harmer, Neil Oronsky, Michelle Lybeck, Harry E Lybeck, James F Brown, Tony R Reid, Corey A Carter
Small cell carcinoma of the vagina is rare, so rare in fact that the total number reported in English-language journals is less than 30. Due to this extremely low incidence, no specific treatment guidelines have been established, and most of what is clinically known is derived from a handful of single case reports. However, as befitting its highly aggressive histologic features, which are reminiscent of small cell lung cancer (SCLC), first-line treatment is modeled after SCLC. Herein is reported the case of a 51-year-old African-American patient with metastatic biopsy-proven small cell carcinoma of the vagina that progressed through multiple therapies: first-line cisplatin and etoposide (making it platinum-resistant) and radiotherapy, followed by the tumor macrophage-stimulating agent RRx-001 in a clinical trial called QUADRUPLE THREAT, which per protocol preceded a mandated rechallenge with cisplatin and etoposide...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28512255/immune-consequences-of-penfluridol-treatment-associated-with-inhibition-of-glioblastoma-tumor-growth
#9
Alok Ranjan, Stephen Wright, Sanjay K Srivastava
Glioblastoma is the most common and lethal brain tumor associated with only 12% median survival rate of patients. Despite the development of advanced surgical, radiation or use of combinations of anti-cancer drugs, treatment for glioblastoma patients is still a challenge. The major contributing factor in glioblastoma progression and resistive nature is its ability to evade the immune surveillance. Hence, modulating the immune system in glioblastoma tumors could be an important strategy for anticancer therapeutics...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28512246/tumor-associated-macrophages-promote-malignant-progression-of-breast-phyllodes-tumors-by-inducing-myofibroblast-differentiation
#10
Yan Nie, Jia-Ning Chen, Di Huang, Yandan Yao, Jiewen Chen, Lin Ding, Jiayi Zeng, Shicheng Su, Xue Chao, Fengxi Su, Herui Yao, Hai Hu, Erwei Song
Myofibroblast differentiation plays an important role in the malignant progression of phyllodes tumor (PT), a fast-growing neoplasm derived from periductal stromal cells of the breast. Macrophages are frequently found in close proximity with myofibroblasts, but it is uncertain whether they are involved in the myofibroblast differentiation during PT progression. Here we show that increased density of tumor associated macrophage (TAM) correlates with malignant progression of PT. We found that TAM stimulated myofibroblast differentiation and promoted the proliferation and invasion of PT cells...
May 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28512240/sting-activation-reverses-lymphoma-mediated-resistance-to-antibody-immunotherapy
#11
Lekh N Dahal, Lang Dou, Khiyam Hussain, Rena Liu, Alexander Earley, Kerry L Cox, Salome Murinello, Ian Tracy, Francesco Forconi, Andrew J Steele, Patrick Duriez, Diego Gomez-Nicola, Jessica L Teeling, Martin J Glennie, Mark S Cragg, Stephen A Beers
Tumors routinely attract and co-opt macrophages to promote their growth, angiogenesis and metastasis. Macrophages are also the key effector cell for monoclonal antibody (mAb) therapies. Here we report that the tumor microenvironment creates an immunosuppressive signature on tumor-associated macrophages (TAM) which favors expression of inhibitory rather than activating Fcγ receptors (FcγR), thereby limiting the efficacy of mAb immunotherapy. We assessed a panel of TLR and STING agonists (a) for their ability to reprogram macrophages to a state optimal for mAb immunotherapy...
May 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28512174/dynamic-changes-in-pd-l1-expression-and-immune-infiltrates-early-during-treatment-predict-response-to-pd-1-blockade-in-melanoma
#12
Ricardo E Vilain, Alexander M Menzies, James S Wilmott, Hojabr Kakavand, Jason Madore, Alexander Guminski, Elizabeth Liniker, Ben Kong, Adam Cooper, Julie R Howle, Robyn P M Saw, Valerie Jakrot, Serigne Lo, John F Thompson, Matteo S Carlino, Richard F Kefford, Georgina V Long, Richard A Scolyer
Disruption of PD-L1/cytotoxic T-cell PD-1 signalling by immune-checkpoint inhibitors improves survival in cancer patients. This study sought to identify changes in tumoral PD-L1 expression and tumor-associated immune cell flux with anti-PD1 therapies in melanoma patients, particularly early during treatment, and correlate them with treatment response<br /><br />Experimental Design: Forty-six tumor biopsies from 23 unresectable AJCC Stage III/IV melanoma patients receiving pembrolizumab/nivolumab were analyzed...
May 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28512150/papers-of-note-in-science-translational-medicine9-389
#13
Leslie K Ferrarelli
This week's articles highlight how tumor-associated macrophages limit the efficacy of PD-1-targeted checkpoint therapy and show that an anti-inflammatory drug may be used to treat lymphedema.
May 16, 2017: Science Signaling
https://www.readbyqxmd.com/read/28511344/anti-inflammatory-effects-of-trans-anethole-in-a-mouse-model-of-chronic-obstructive-pulmonary-disease
#14
Ka Young Kim, Hui Su Lee, Geun Hee Seol
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease that is generally characterized by progressive and irreversible airflow obstruction and alveolar destruction. Long-term treatment with current medications has been associated with various adverse effects, indicating a need for alternative approaches for the prevention and treatment of COPD. This study investigated the mechanism underlying the effects of trans-anethole in a mouse model of COPD induced by porcine pancreatic elastase (PPE) and lipopolysaccharide (LPS)...
May 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28509629/nanoparticle-based-delivery-enhances-anti-inflammatory-effect-of-low-molecular-weight-heparin-in-experimental-ulcerative-colitis
#15
Tawfek Yazeji, Brice Moulari, Arnaud Beduneau, Valentin Stein, Dirk Dietrich, Yann Pellequer, Alf Lamprecht
Epithelial administration of low molecular weight heparin (LMWH) has proven its therapeutic efficiency in ulcerative colitis (UC) but still lacks of a sufficiently selective drug delivery system. Polymeric nanoparticles were used here not only to protect LMWH from intestinal degradation but also to provide targeted delivery to inflamed tissue in experimental colitis mice. LMWH was associated with polymethacrylate nanoparticles (NP) type A (PEMT-A) or type B (PEMT-B) of a size: 150 nm resulting in a maximum drug loading: 0...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28508193/neutrophil-depletion-improves-diet-induced-non-alcoholic-fatty-liver-disease-in-mice
#16
Rongying Ou, Jia Liu, Mingfen Lv, Jingying Wang, Jinmeng Wang, Li Zhu, Liang Zhao, Yunsheng Xu
PURPOSE: Non-alcoholic fatty liver disease is highly associated with morbidity and mortality in population. Although studies have already demonstrated that the immune response plays a pivotal role in the development of non-alcoholic fatty liver disease, the comprehensive regulation is unclear. Therefore, present study was carried out to investigate the non-alcoholic fatty liver disease development under neutrophil depletion. METHODS: To achieve the aim of the study, C57BL/6 J mice were fed with high fat diet for 6 weeks before treated with neutrophil deplete antibody 1A8 or isotype control (200 μg/ mouse every week) for another 4 weeks...
April 6, 2017: Endocrine
https://www.readbyqxmd.com/read/28507813/deep-exploration-of-the-immune-infiltrate-and-outcome-prediction-in-testicular-cancer-by-quantitative-multiplexed-immunohistochemistry-and-gene-expression-profiling
#17
Peter J Siska, Romany A N Johnpulle, Alice Zhou, Jennifer Bordeaux, Ju Young Kim, Bashar Dabbas, Naveen Dakappagari, Jeffrey C Rathmell, W Kimryn Rathmell, Alicia K Morgans, Justin M Balko, Douglas B Johnson
Platinum-based chemotherapy is usually curative for patients with testicular germ cell tumors (TGCT), but a subset of patients experience disease progression and poor clinical outcomes. Here, we tested whether immune profiling of TGCT could identify novel prognostic markers and therapeutic targets for this patient cohort. We obtained primary and metastatic TGCT samples from one center. We performed immune profiling using multiplexed fluorescence immunohistochemistry (FIHC) for T-cell subsets and immune checkpoints, and targeted gene expression profiling (Nanostring nCounter Immune panel)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507810/tie-2-expressing-monocytes-in-human-cancers
#18
Riccardo Turrini, Angélique Pabois, Ioannis Xenarios, George Coukos, Jean-François Delaloye, Marie-Agnès Doucey
Tumor-associated macrophages (TAM) are well known as a key player in the tumor microenvironment, which support cancer progression. More recently, a lineage of monocytes characterized by the expression of the TIE-2/Tek angiopoietin receptor identified a subset of circulating and tumor-associated monocytes endowed with proangiogenic activity. TIE-2 expressing monocytes (TEM) were found both in humans and mice. Here, we review the phenotypes and functions of TEM reported so far in human cancer and their potential use as markers of cancer progression and metastasis...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507808/pro-necrotic-molecules-impact-local-immunosurveillance-in-human-breast-cancer
#19
Gautier Stoll, Yuting Ma, Heng Yang, Oliver Kepp, Laurence Zitvogel, Guido Kroemer
Necrosis culminates in spilling cellular content through the permeabilized plasma membrane, thereby releasing potentially immunostimulatory molecules in the pericellular space of dead cells. Accordingly, molecules involved in necroptotic signaling, such as receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and mixed lineage kinase-like (MLKL) have been found to stimulate anticancer immune responses in mouse models of chemotherapy. mRNAs encoding prominent pro-necrotic gene products (RIPK1, RIPK3, MLKL, PGAM5 and DFNA5) were correlated with immune-related metagenes in several cancer types (breast, colorectal, lung, ovary, melanoma), revealing the strongest associations in breast cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28504999/tumor-microenvironment-and-checkpoint-molecules-in-primary-cutaneous-diffuse-large-b-cell-lymphoma-new-therapeutic-targets
#20
Christina Mitteldorf, Arbeneshe Berisha, Monique C Pfaltz, Sigrid M C Broekaert, Michael P Schön, Katrin Kerl, Werner Kempf
Programmed death ligand 1 (PD-L1) is expressed by 20% to 57% of systemic diffuse large B cell lymphomas (DLBCLs). PD-L1 expression in primary cutaneous DLBCL (pcDLBCL) has not been studied so far. Sixteen paraffin-embedded tissue samples of pcDLBCL (13 leg type [LT], 3 others [OT]) were investigated for PD-1, PD-L1, and CD33 expression and the cellular composition of the tumor microenvironment, focusing on myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages. Membrane-bound PD-L1 expression by the tumor cells was observed in all samples, albeit to a variable extent (19...
May 12, 2017: American Journal of Surgical Pathology
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