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Tumor infiltrating neutrophils

Jinʼe Liu, Xiaoxue Xie, Chunxiao Xuan, Tingting Li, Lanlan Wang, Lianghong Teng, Jun Liu
V-domain immunoglobulin suppressor of T-cell activation (VISTA) is constitutively expressed in hematopoietic lineage and is highly up-regulated in tumor infiltrated myeloid cells and regulatory T cells in animal models. However, its expression in human pancreatic tumor microenvironment remains unknown. In this research, we aimed at the expression of VISTA in human pancreatic cancer samples. METHODS: We performed immunohistochemistry to determine VISTA expression in human pancreatic cancer samples...
May 15, 2018: Pancreas
Peng-Fei Wang, Hong-Qing Cai, Chuan-Bao Zhang, Yan-Michael Li, Xiang Liu, Jing-Hai Wan, Tao Jiang, Shou-Wei Li, Chang-Xiang Yan
BACKGROUND: Immune checkpoint inhibitors have been shown to promote antitumor immunity and achieve durable tumor remissions. However, certain tumors are refractory to current immunotherapy. These negative results encouraged us to uncover other therapeutic targets and strategies. PTPN2 (protein tyrosine phosphatase, non-receptor type 2) has been newly identified as an immunotherapy target. Loss of PTPN2 sensitizes the tumor to immunotherapy via IFNγ signaling. METHODS: Here, we investigated the relationship between PTPN2 mRNA levels and clinical characteristics in gliomas...
May 15, 2018: Journal of Neuroinflammation
Qinlong Liu, Hasibur Rehman, Yasodha Krishnasamy, John J Lemasters, Zhi Zhong
Pulmonary complications frequently occur after liver transplantation and are often life-threatening. Thus, we investigated whether hepatic ischemic preconditioning (IP) attenuates acute lung injury (ALI) after small-for-size liver transplantation. Rat livers were explanted after 9-min ischemia plus 5-min reperfusion, reduced to 50% of original size ex vivo , and implanted into recipients with approximately twice the donor body weight, resulting in quarter-size liver grafts (QSG). After QSG transplantation, hepatic Toll-like receptor 4 (TLR4) and tumor necrosis factor-α (TNFα ) expression increased markedly and high mobility group box-1 (HMGB1), an endogenous damage-associated molecular pattern molecule (DAMP), was released from QSG into the blood...
2018: International Journal of Physiology, Pathophysiology and Pharmacology
Bo Mei, Song Yang, Yuan Yue, Jian Hou, Keke Wang, Guangxian Chen, Mengya Liang, Zhongkai Wu
OBJECTIVE: Cardiopulmonary bypass (CPB) might induce systemic inflammatory responses that cause acute injuries to multiple organs. However, no direct evidence exists to determine whether CPB leads to adrenal cortex injury or to describe its underlying mechanism. METHODS: Twelve healthy adult beagles were randomly assigned into control and CPB groups. After cannulation, mild hypothermia CPB was performed in the CPB group but not in the control group. The serum concentrations of various cytokines, cortisol, and aldosterone were assessed...
April 11, 2018: Journal of Thoracic and Cardiovascular Surgery
Yufu Wang, Tianyi Fang, Lining Huang, Hao Wang, Lei Zhang, Zhidong Wang, Yunfu Cui
CD177 is considered to represent neutrophils. We analyzed mRNA expression level of CD177 and clinical follow-up survey of PDAC to estimate overall survival (OS) from Gene Expression Omnibus (GEO) dataset (GSE21501, containing samples from 102 PDAC patients) by R2 platform ( We also analyzed correlated genes of CD177 by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to predict the potential relationship between neutrophils and prognosis of PDAC. We then performed hematoxylin and eosin (H&E) staining and immunohistochemical staining of surgical specimens to verify infiltration of neutrophils in PDAC tissues...
May 5, 2018: Biochemical and Biophysical Research Communications
Jie Wang, Xiaobo Bo, Tao Suo, Han Liu, Xiaoling Ni, Sheng Shen, Min Li, Jiejie Xu, Houbao Liu, Yueqi Wang
Tumor-infiltrating neutrophils (TINs) perform quite significant but opposite functions in different cancers, and its function in biliary cancer has not been fully characterized. To investigate the prognostic significance of TINs in biliary cancer, a training set (n=118) and a validation set (n=127) were involved in this study. TINs were evaluated by immunohistochemical staining of CD66b, and then defined as low (neutrophils<18/HPF) versus high (neutrophils ≥18/HPF). Kaplan-Meier curve, cox proportional hazards models and receiver operating characteristic curve were used to assess the prognostic significance...
May 3, 2018: Cancer Science
Neil L Berinstein, Michael McNamara, Ariane Nguyen, James Egan, Gregory T Wolf
IRX-2 is an injectable cancer immunotherapy composed of cytokines purified from stimulated normal-donor peripheral blood mononuclear cells. In a phase 2a trial (n = 27), neoadjuvant IRX-2 significantly increased lymphocyte infiltration (LI) into resected head and neck tumors and was associated with changes in fibrosis and necrosis. Event-free survival was 65% at 2 years, and overall survival 65% at 5 years. Overall survival was longer for patients with LI greater versus lower than the median. This substudy of the mechanisms responsible for the increase in LI with neoadjuvant IRX-2 employed multiplex immunohistochemistry (IHC) and transcriptome analysis to interrogate matched pre- and post-treatment tumor specimens from 7 available phase 2a trial patients...
2018: Oncoimmunology
Li-Long Pan, Yuan-Yuan Deng, Ruxing Wang, Chengfei Wu, Jiahong Li, Wenying Niu, Qin Yang, Madhav Bhatia, Gudmundur H Gudmundsson, Birgitta Agerberth, Julien Diana, Jia Sun
Acute pancreatitis (AP) is one common clinical acute abdominal disease, for which specific pharmacological or nutritional therapies remain elusive. Lactose, a macronutrient and an inducer of host innate immune responses, possesses immune modulatory functions. The current study aimed to investigate potential modulatory effects of lactose and the interplay between the nutrient and pancreatic immunity during experimentally induced AP in mice. We found that either prophylactic or therapeutic treatment of lactose time-dependently reduced the severity of AP, as evidenced by reduced pancreatic edema, serum amylase levels, and pancreatic myeloperoxidase activities, as well as by histological examination of pancreatic damage...
2018: Frontiers in Immunology
Karolina Najder, Boris Musset, Otto Lindemann, Etmar Bulk, Albrecht Schwab, Benedikt Fels
Neutrophil granulocytes are exposed to widely varying microenvironmental conditions when pursuing their physiological or pathophysiological functions such as fighting invading bacteria or infiltrating cancer tissue. Examples for harsh environmental challenges include among others mechanical shear stress during the recruitment from the vasculature or the hypoxic and acidotic conditions within the tumor microenvironment. Chemokine gradients, reactive oxygen species, pressure, matrix elasticity, and temperature can be added to the list of potential challenges...
May 1, 2018: Pflügers Archiv: European Journal of Physiology
Jae Eun Choi, Anna Di Nardo
The epidermis closely interacts with nerve endings, and both epidermis and nerves produce substances for mutual sustenance. Neuropeptides, like substance P (SP) and calcitonin gene-related protein (CGRP), are produced by sensory nerves in the dermis; they induce mast cells to release vasoactive amines that facilitate infiltration of neutrophils and T cells. Some receptors are more important than others in the generation of itch. The Mas-related G protein-coupled receptors (Mrgpr) family as well as transient receptor potential ankyrin 1 (TRPA1) and protease activated receptor 2(Par2) have important roles in itch and inflammation...
April 30, 2018: Seminars in Immunopathology
Abderrahim Nemmar, Suhail Al-Salam, Priya Yuvaraju, Sumaya Beegam, Badreldin H Ali
Water pipe smoking is a tobacco smoking method commonly used in Eastern countries and is gaining popularity in Europe and North America, in particular among adolescents and young adults. Several clinical and experimental studies have reported that exposure to water pipe smoke (WPS) induces lung inflammation and impairment of pulmonary function. However, the mechanisms of such effects are not understood, as are data on the possible palliative effect of exercise training. The present study evaluated the effects of regular aerobic exercise training (treadmill: 5 days/week, 40 min/day) on subchronic exposure to WPS (30 minutes/day, 5 days/week for 2 months)...
2018: Oxidative Medicine and Cellular Longevity
Hung-Chen Lee, Chia-Chih Liao, Yuan-Ji Day, Jiin-Tarng Liou, Allen H Li, Fu-Chao Liu
Acetaminophen (APAP) overdose results in the production of reactive oxygen species (ROS), hepatocyte necrosis, and cell death, and leads to acute liver failure. Interleukin-17 (IL-17), a pro-inflammatory cytokine, plays a key role in the recruitment of neutrophils into sites of inflammation and subsequent damage after liver ischemia-reperfusion injury. In this study, we employed IL-17 knockout (KO) mice to investigate the role of IL-17 in APAP-induced hepatotoxicity. IL-17 wide type (WT) and IL-17 KO mice received an intraperitoneal injection of APAP (300 mg/kg)...
April 21, 2018: Toxicology Letters
Hwajin Kim, So Ra Kim, Jihyun Je, Kyuho Jeong, Sooji Kim, Hye Jung Kim, Ki Churl Chang, Sang Won Park
Activation of the α7 nicotinic acetylcholine receptor (α7nAChR) has been shown to attenuate excessive inflammation by inhibiting proinflammatory cytokines during ischemia-reperfusion (IR) injury; however, the underlying kidney-specific molecular mechanisms remain unclear. The protective action of α7nAChR against renal IR injury was investigated using a selective α7nAChR agonist and antagonist. α7nAChR activation reduced plasma creatinine levels and tubular cell damage, whereas α7nAChR inhibition aggravated the IR-induced phenotype...
April 20, 2018: Experimental & Molecular Medicine
Nataliya Rohr-Udilova, Florian Klinglmüller, Rolf Schulte-Hermann, Judith Stift, Merima Herac, Martina Salzmann, Francesca Finotello, Gerald Timelthaler, Georg Oberhuber, Matthias Pinter, Thomas Reiberger, Erika Jensen-Jarolim, Robert Eferl, Michael Trauner
Tumor-infiltrating immune cells are highly relevant for prognosis and identification of immunotherapy targets in hepatocellular carcinoma (HCC). The recently developed CIBERSORT method allows immune cell profiling by deconvolution of gene expression microarray data. By applying CIBERSORT, we assessed the relative proportions of immune cells in 41 healthy human livers, 305 HCC samples and 82 HCC adjacent tissues. The obtained immune cell profiles provided enumeration and activation status of 22 immune cell subtypes...
April 18, 2018: Scientific Reports
Xinglong Qu, Ying Tang, Shucheng Hua
The inflammation is the protective response of the body against various harmful stimuli; however, the aberrant and inappropriate activation tends to become harmful. The acute inflammatory response tends to resolved once the offending agent is subside but this acute response becomes chronic in nature when the body is unable to successfully neutralized the noxious stimuli. This chronic inflammatory microenvironment is associated with the release of various pro-inflammatory and oncogenic mediators such as nitric oxide (NO), cytokines [IL-1β, IL-2, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)], growth factor, and chemokines...
2018: Frontiers in Immunology
Soichiro Hiramatsu, Hiroaki Tanaka, Junya Nishimura, Chie Sakimura, Tatsuro Tamura, Takahiro Toyokawa, Kazuya Muguruma, Masakazu Yashiro, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: Tumor-Associated Neutrophils (TANs) may be able to induce lymphangiogenesis and angiogenesis, although the detailed roles of TANs remain unclear. The Neutrophil-Lymphocyte Ratio (NLR) is an inflammation-based prognostic factor for gastric cancer. This study aimed to investigate the distribution of CD15+ neutrophils in the primary tumor and Tumor-Draining Lymph Nodes (TDLNs), and to examine the association of TANs with the clinicopathological features (including NLR) of patients with gastric cancer...
April 16, 2018: BMC Immunology
Soichiro Sasaki, Tomohisa Baba, Hayato Muranaka, Yamato Tanabe, Chiaki Takahashi, Seiichi Matsugo, Naofumi Mukaida
Adjuvant chemotherapy is used for human breast cancer patients, even after curative surgery of primary tumor, in order to prevent tumor recurrence primarily as a form of metastasis. However, anti-cancer drugs can accelerate metastasis in several mouse metastasis models. Hence, we examined the effects of post-surgical administration with 5-fluorouracil (5-FU), doxorubicin, and cyclophosphamide, on lung metastasis process, which developed after the resection of the primary tumor arising from the orthotopic injection of a mouse triple-negative breast cancer cell line, 4T1...
April 11, 2018: Molecular Cancer Therapeutics
Rita Brines, Laura Catalán, Maria José Alcaraz, Maria Luisa Ferrándiz
Heme oxygenase-1 (HO-1) is induced by many stimuli to modulate the activation and function of different cell types during innate immune responses. Although HO-1 has shown anti-inflammatory effects in different systems, there are few data on the contribution of myeloid HO-1 and its role in inflammatory processes is not well understood. To address this point, we have used HO-1M-KO mice with myeloid-restricted deletion of HO-1 to specifically investigate its influence on the acute inflammatory response to zymosan in vivo ...
2018: Oxidative Medicine and Cellular Longevity
Linjie Zhao, Shuang Huang, Shenglin Mei, Zhengnan Yang, Lian Xu, Nianxin Zhou, Qilian Yang, Qiuhong Shen, Wei Wang, Xiaobing Le, Wayne Bond Lau, Bonnie Lau, Xin Wang, Tao Yi, Xia Zhao, Yuquan Wei, Margaret Warner, Jan-Åke Gustafsson, Shengtao Zhou
Metastases constitute the greatest causes of deaths from cancer. However, no effective therapeutic options currently exist for cancer patients with metastasis. Estrogen receptor β (ERβ), as a member of the nuclear receptor superfamily, shows potent tumor-suppressive activities in many cancers. To investigate whether modulation of ERβ could serve as a therapeutic strategy for cancer metastasis, we examined whether the selective ERβ agonist LY500307 could suppress lung metastasis of triple-negative breast cancer (TNBC) and melanoma...
April 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
Marion Humbert, Leslie Guery, Dale Brighouse, Sylvain Lemeille, Stephanie Hugues
Cancer immunotherapies utilize distinct mechanisms to harness the power of the immune system to eradicate cancer cells. Therapeutic vaccines, aimed at inducing active immune responses against an existing cancer, are highly dependent on the immunological microenvironment, where many immune cell types display high levels of plasticity and, depending on the context, promote very different immunological outcomes. Among them, plasmacytoid dendritic cells (pDC), known to be highly immunogenic upon inflammation, are maintained in a tolerogenic state by the tumor microenvironment...
March 27, 2018: Cancer Research
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