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macrophage and TAM

Sofia Sousa, Jorma Määttä
This overview addresses the recent research developments in the role of tumour-associated macrophages (TAM) in bone metastasis biology and management of breast and prostate cancer as well as in primary and lung metastatic osteosarcoma. Immunosuppressive M2-type TAMs have been shown to associate with poor prognosis. Throughout their life cycle, macrophages (Macs) can adapt to environmental cues and influence the surroundings by secreting different cytokines and enzymes crucial to matrix remodelling, infection fighting, immune regulation and/or inflammation...
September 2016: Journal of Bone Oncology
Yoshihiro Komohara, Motohiro Takeya
Many non-tumour host cells such as inflammatory cells, fibroblasts and endothelial cells are present in the tumour microenvironment and affect the malignant potential and chemo-resistance of the tumour cells. Macrophages and fibroblasts are the main components of infiltrating stromal cells and are referred to as tumour-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), respectively. TAMs and CAFs are reported to be involved in tumour progression, although their functions change to those of an anti-tumour phenotype under specific conditions...
October 18, 2016: Journal of Pathology
Qinyi Zhu, Xiaoli Wu, Yueqian Wu, Xipeng Wang
Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. Inflammatory cells in the EOC microenvironment play a key role in tumor progression. In the present study, we investigated the mechanism of the accumulation of regulatory T cells (Tregs) induced by interleukin-10 (IL-10) derived from tumor-associated macrophages (TAMs) in the EOC microenvironment. The frequency of Tregs and TAMs was detected by immunofluorescence in 40 EOC tissues and 20 benign ovarian tumors, as well as the expression of IL-10 which was assessed by immunohistochemistry...
September 28, 2016: Oncology Reports
Baoping Guo, Hong Cen, Xiaohong Tan, Qing Ke
BACKGROUND: The prognostic significance of tumor-associated macrophages (TAM) in adult classical Hodgkin lymphoma (cHL) remains controversial. Here, we report a meta-analysis of the association of CD68 and CD163 infiltration on the clinical outcome of adult cHL. METHODS: A comprehensive search to identify relevant articles was performed in PubMed, Embase, and Google Scholar on January 31, 2016. Using the fixed effect or random effects model of DerSimonian and Laird, hazard ratios (HR) or odds ratios (OR) with 95 % confidence intervals (CIs) were used as the effect size estimate...
October 17, 2016: BMC Medicine
Lucy Ireland, Almudena Santos, Muhammad S Ahmed, Carolyn Rainer, Sebastian R Nielsen, Valeria Quaranta, Ulrike Weyer-Czernilofsky, Danielle D Engle, Pedro Perez-Mancera, Sarah E Coupland, Azzam F Taktak, Thomas Bogenrieder, David A Tuveson, Fiona Campbell, Michael C Schmid, Ainhoa Mielgo
Tumor associated macrophages (TAM) and myofibroblasts are key drivers in cancer that are associated with drug resistance in many cancers, including pancreatic ductal adenocarcinoma (PDAC). However, our understanding of the molecular mechanisms by which TAM and fibroblasts contribute to chemoresistance is unclear. In this study, we found that TAM and myofibroblasts directly support chemoresistance of pancreatic cancer cells by secreting insulin-like growth factors 1 and 2 (IGF), which activate Insulin/IGF receptors on pancreatic cancer cells...
October 14, 2016: Cancer Research
Hoibin Jeong, Seoyeon Bok, Beom-Ju Hong, Hyung-Seok Choi, G-One Ahn
Recent advancement in the radiotherapy technology has allowed conformal delivery of high doses of ionizing radiation precisely to the tumors while sparing large volume of the normal tissues, which have led to better clinical responses. Despite this technological advancement many advanced tumors often recur and they do so within the previously irradiated regions. How could tumors recur after receiving such high ablative doses of radiation? In this review, we outlined how radiation can elicit anti-tumor responses by introducing some of the cytokines that can be induced by ionizing radiation...
September 2016: Blood Research
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...
October 10, 2016: Journal of Clinical Investigation
Piotr Donizy, Maciej Kaczorowski, Przemyslaw Biecek, Agnieszka Halon, Teresa Szkudlarek, Rafal Matkowski
GOLPH2 and GOLPH3 are Golgi-related proteins associated with aggressiveness and progression of a number of cancers. Their prognostic significance in melanoma has not yet been analyzed. We performed immunohistochemical analysis for GOLPH2 and GOLPH3 in 20 normal skin, 30 benign nevi and 100 primary melanoma tissue samples and evaluated their expression in three compartments: cancer cells, tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs). High levels of both proteins in melanoma cells were associated with characteristics of aggressive disease, and shorter disease-free survival (DFS) and cancer-specific overall survival (CSOS)...
October 1, 2016: International Journal of Molecular Sciences
Armando Rojas, Carolina Añazco, Paulina Araya
Tumor-associated macrophages (TAMs) are key elements in orchestrating host responses inside tumor stroma. This population may undergo a polarized activation process, thus rendering a heterogeneous spectrum of phenotypes, where the classically activated type 1 macrophages (M1) and the alternative activated type 2 macrophages (M2) represent two extreme phenotypes. In this commentary, based on very recent research findings, we intend to highlight how complex could be the crosstalk among all components of tumor stroma, where the coexistence of non-natural partners may even skew the canonical responses that we can expect...
October 3, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Shuting Jiang, Yuehong Yang, Min Fang, Xianglang Li, Xiuxue Yuan, Jingping Yuan
Considering the crucial significance of the tumor microenvironment in cancer development and progression, the present study aimed to investigate the changes in macrophages and angiogenesis during the cervical cancer (CC) progression process from chronic cervicitis to cervical intraepithelial neoplasia grades I-III (CIN I-III) to CC. This investigation included quantitative analysis and assessment of the spatial associations between tumor-associated macrophages (TAMs) and tumor neo-vessels. The conventional immunohistochemistry staining technique was used to detect cluster of differentiation (CD)68 and CD105 biomarker expression for TAMs and tumor neo-vessels, respectively...
October 2016: Oncology Letters
Ran Afik, Ehud Zigmond, Milena Vugman, Mordehay Klepfish, Elee Shimshoni, Metsada Pasmanik-Chor, Anjana Shenoy, Elad Bassat, Zamir Halpern, Tamar Geiger, Irit Sagi, Chen Varol
Tumor-associated macrophages (TAMs) promote tumor development, invasion, and dissemination by various mechanisms. In this study, using an orthotopic colorectal cancer (CRC) model, we found that monocyte-derived TAMs advance tumor development by the remodeling of its extracellular matrix (ECM) composition and structure. Unbiased transcriptomic and proteomic analyses of (a) TAM-abundant and -deficient tumor tissues and (b) sorted tumor-associated and -resident colonic macrophage subpopulations defined a distinct TAM-induced ECM molecular signature composed of an ensemble of matricellular proteins and remodeling enzymes they provide to the tumor microenvironment...
October 3, 2016: Journal of Experimental Medicine
Anna Malawista, Xiaomei Wang, Mark Trentalange, Heather G Allore, Ruth R Montgomery
The TAM receptors (Tyro3, Axl, and Mer) are a family of homologous receptor-tyrosine kinases that inhibit Toll-like receptor signaling to regulate downstream pathways and restore homeostasis. TAM triple mutant mice (Tyro3(-/-), Axl(-/-), Mer(-/-)) have elevated levels of pro-inflammatory cytokines and are prone to developing lymphoproliferative disorders and autoimmunity. Understanding differential expression of TAM receptors among human subjects is critical to harnessing this pathway for therapeutic interventions...
2016: Macrophage
Wing Yin Cheng, HoangDinh Huynh, Peiwen Chen, Samuel Peña-Llopis, Yihong Wan
Tumor-associated macrophage (TAM) significantly contributes to cancer progression. Human cancer is enhanced by PPARγ loss-of-function mutations, but inhibited by PPARγ agonists such as TZD diabetes drugs including rosiglitazone. However, it remains enigmatic whether and how macrophage contributes to PPARγ tumor-suppressive functions. Here we report that macrophage PPARγ deletion in mice not only exacerbates mammary tumor development but also impairs the anti-tumor effects of rosiglitazone. Mechanistically, we identify Gpr132 as a novel direct PPARγ target in macrophage whose expression is enhanced by PPARγ loss but repressed by PPARγ activation...
October 3, 2016: ELife
Makito Miyake, Shunta Hori, Yosuke Morizawa, Yoshihiro Tatsumi, Yasushi Nakai, Satoshi Anai, Kazumasa Torimoto, Katsuya Aoki, Nobumichi Tanaka, Keiji Shimada, Noboru Konishi, Michihiro Toritsuka, Toshifumi Kishimoto, Charles J Rosser, Kiyohide Fujimoto
Tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) are reported to be associated with poor prognosis, depending on their pro-tumoral roles. Current knowledge of TAMs and CAFs in the tumor microenvironment of urothelial cancer of the bladder (UCB) is limited. Therefore, we investigated the paracrine effect induced by TAMs and CAFs in the tumor microenvironment of human UCB. For this, we first carried out immunohistochemical analysis for CXCL1, CD204 (TAM marker), αSMA (CAF marker), E-cadherin, and MMP2 using 155 UBC tissue samples...
October 2016: Neoplasia: An International Journal for Oncology Research
G Galletti, F Caligaris-Cappio, M T S Bertilaccio
The development and progression of chronic B-cell tumors depend on a complex microenvironmental network of cells that include monocyte-derived macrophages. In chronic lymphocytic leukemia (CLL) the survival of malignant cells is supported in vitro by nurse-like cells, which differentiate from CD14(+) monocytes and have been identified as tumor-associated macrophages (TAMs). The role of the monocyte/macrophage lineage in CLL has been extensively studied in vitro, but only recently has been investigated in in vivo models...
October 14, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Baoshi Chen, Tingyu Liang, Pei Yang, Haoyuan Wang, Yanwei Liu, Fan Yang, Gan You
OBJECTIVE: To identify a gene-based signature as a novel prognostic model in lower grade gliomas. RESULTS: A gene signature developed from HOXA7, SLC2A4RG and MN1 could segregate patients into low and high risk score groups with different overall survival (OS), and was validated in TCGA RNA-seq and GSE16011 mRNA array datasets. Receiver operating characteristic (ROC) was performed to show that the three-gene signature was more sensitive and specific than histology, grade, age, IDH1 mutation and 1p/19q co-deletion...
September 22, 2016: Oncotarget
Florian Finkernagel, Silke Reinartz, Sonja Lieber, Till Adhikary, Annika Wortmann, Nathalie Hoffmann, Tim Bieringer, Andrea Nist, Thorsten Stiewe, Julia M Jansen, Uwe Wagner, Sabine Müller-Brüsselbach, Rolf Müller
Macrophages occur as resident cells of fetal origin or as infiltrating blood monocyte-derived cells. Despite the critical role of tumor-associated macrophages (TAMs) in tumor progression, the contribution of these developmentally and functionally distinct macrophage subsets and their alteration by the tumor microenvironment are poorly understood. We have addressed this question by comparing TAMs from human ovarian carcinoma ascites, resident peritoneal macrophages (pMPHs) and monocyte-derived macrophages (MDMs)...
September 21, 2016: Oncotarget
Jing Liang, Xiaolin Liu, Qi Xie, Guoling Chen, Xingyu Li, Yanrui Jia, Beibei Yin, Xun Qu, Yan Li
OBJECTIVE: To investigate the antitumor effect of endostatin combined with tumor antigen-pulsed dendritic cell (DC)-T cell therapy on lung cancer. METHODS: Transplanted Lewis lung cancer (LLC) models of C57BL/6 mice were established by subcutaneous injection of LLC cells in left extremity axillary. Tumor antigen-pulsed DC-T cells from spleen cells and bone of mice were cultured in vitro. Tumor-bearing mice were randomly divided into three groups, including DC-T+endostatin group, DC-T group, and phosphate-buffered saline (PBS) control group...
August 2016: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
Karolina Okła, Iwona Wertel, Grzegorz Polak, Justyna Surówka, Anna Wawruszak, Jan Kotarski
Cancers are complex masses of malignant cells and nonmalignant cells that create the tumor microenvironment (TME). Non-transformed cells of the TME such as tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) have been observed in the TME of ovarian cancer (OC) patients. Although these subsets may contribute to each step of carcinogenesis and are commonly associated with poor prognosis, still little is known about creation of the protumor microenvironment in OC. In this review, we focused on the nature and prognostic significance of TAMs and MDSCs in OC patients...
September 19, 2016: International Reviews of Immunology
Zhao Li, Xiaobing Liu, Rongbin Guo, Pengfei Wang
CD4(+)Foxp3(-) type 1 regulatory T (Tr1) cells are potent producers of interleukin 10 (IL-10) and transforming growth factor beta (TGF-β), through which they suppress pathogenic inflammation and autoimmune responses. The role of Tr1 response in glioblastoma multiforme (GBM) is still unclear. Here, we examined the frequency, phenotype, induction mechanism, and function of Tr1 cells in GBM patients. Compared to healthy controls, GBM patients presented significantly higher frequency of Tr1 cells in peripheral blood...
September 16, 2016: International Journal of Biochemistry & Cell Biology
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