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macrophage and TAM

Q L Gui, Y S Wang, S Huang, Y Wan, H P Wang, Z G Zhu, M M Li, H Y Zhu, Q S Tao, Y Y Shen, Q Zhang, H Qin
Objective: To investigate the clinical significance of tumor associated macrophages (TAM) in multiple myeloma (MM) and the relationship with angiogenesis and immunosuppression. Methods: Seventy cases of MM patients diagnosed from August 2015 to June 2017 were enrolled in the study as experimental group, 20 cases of benign hematological diseases (13 with iron deficiency anemia and 7 with megaloblastic anemia) patients as control group. Immunohistochemical method was used to detect the expression of CD163, CD34 and VEGF in bone marrow samples, and flow cytometry was used to detect the proportion of regulatory T cell (Treg cells), ELISA was used to detect the level of IL-10, and the clinical features were analyzed...
February 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Honglin Jin, Chao Wan, Zhenwei Zou, Guifang Zhao, Lingling Zhang, Yuanyuan Geng, Tong Chen, Ai Huang, Fagang Jiang, Jue-Ping Feng, Jonathan F Lovell, Jing Chen, Gang Wu, Kunyu Yang
Immunosuppressive tumor microenvironments (TMEs) create tremendous obstacles for an effective cancer therapy. Herein, we developed a melittin-RADA32 hybrid peptide hydrogel loaded with doxorubicin (DOX) for a potent chemoimmunotherapy against melanoma through the active regulation of TMEs. The formed melittin-RADA32-DOX (MRD) hydrogel has an interweaving nanofiber structure and exhibits excellent biocompatibility, controlled drug release properties both in vitro and in vivo, and an enhanced killing effect to melanoma cells...
March 20, 2018: ACS Nano
Chunmei Piao, Wen-Mei Zhang, Tao-Tao Li, Cong-Cong Zhang, Shulan Qiu, Yan Liu, Sa Liu, Ming Jin, Li-Xin Jia, Wen-Chao Song, Jie Du
Inflammatory cells such as macrophages can play a pro-tumorigenic role in the tumor stroma. Tumor-associated macrophages (TAMs) generally display an M2 phenotype with tumor-promoting activity; however, the mechanisms regulating the TAM phenotype remain unclear. Complement 5a (C5a) is a cytokine-like polypeptide that is generated during complement system activation and is known to promote tumor growth. Herein, we investigated the role of C5a on macrophage polarization in colon cancer metastasis in mice. We found that deficiency of the C5a receptor (C5aR) severely impairs the metastatic ability of implanted colon cancer cells...
March 15, 2018: Experimental Cell Research
Delphine Lumbroso, Soaad Soboh, Avi Maimon, Sagie Schif-Zuck, Amiram Ariel, Tal Burstyn-Cohen
The complete resolution of inflammation requires the uptake of apoptotic polymorphonuclear cells (PMN) by local macrophages (efferocytosis) and the consequent reprogramming of the engulfing phagocytes to reparative and pro-resolving phenotypes. The tyrosine kinase receptors TYRO3, AXL, and MERTK (collectively named TAM) are fundamental mediators in regulating inflammatory responses and efferocytosis. Protein S (PROS1) is a ligand for all TAM receptors that mediates various aspects of their activity. However, the involvement of PROS1 in the resolution of inflammation is incompletely understood...
2018: Frontiers in Immunology
Takuya Tsubaki, Tetsuya Kadonosono, Shimon Sakurai, Tadashi Shiozawa, Toshiki Goto, Shiori Sakai, Takahiro Kuchimaru, Takeharu Sakamoto, Hitomi Watanabe, Gen Kondoh, Shinae Kizaka-Kondoh
The immunosuppressive tumor microenvironment is a hallmark of cancer. Myeloid-derived suppressor cells (MDSCs) are CD11b+ Gr-1+ tumor-infiltrating immature myeloid cells that strongly mediate tumor immunosuppression. The CD11b+ Gr-1+ cells are a heterogeneous cell population, and the impacts of each subpopulation on tumor progression are not yet completely understood. In the present study, we identified a novel subpopulation of CD11b+ Gr-1+ cells from murine lung carcinoma tumors according to their strongly adherent abilities...
February 16, 2018: Oncotarget
Hirokazu Sadahiro, Kyung-Don Kang, Justin T Gibson, Mutsuko Minata, Hai Yu, Junfeng Shi, Rishi Raj Chhipa, Zhihong Chen, Songjia Lu, Yannick Simoni, Takuya Furuta, Hemragul Sabit, Suojun Zhang, Soniya Bastola, Shinobu Yamaguchi, Heba Allah Alsheikh, Svetlana Komarova, Jun Wang, Sung-Hak Kim, Dolores Hambardzumyan, Xinghua Lu, Evan W Newell, Biplab Dasgupta, Mitsutoshi Nakada, Ly James Lee, Louis B Nabors, Lyse A Norian, Ichiro Nakano
Glioblastoma (GBM) is a lethal disease with no effective therapies available. We previously observed upregulation of the TAM (Tyro-3, Axl, and Mer) receptor tyrosine kinase family member AXL in mesenchymal GBM and showed that knockdown of AXL induced apoptosis of mesenchymal, but not proneural, glioma sphere cultures (GSC). In this study, we report that BGB324, a novel small molecule inhibitor of AXL, prolongs the survival of immunocompromised mice bearing GSC-derived mesenchymal GBM-like tumors. We show that protein S (PROS1), a known ligand of other TAM receptors, was secreted by tumor-associated macrophages/microglia and subsequently physically associated with and activated AXL in mesenchymal GSC...
March 12, 2018: Cancer Research
Jie Wang, Lina Yang, Xiaohe Mao, Zaiye Li, Xiaoyu Lin, Canhua Jiang
It has been shown that the peripheral blood mononuclear cells (PBMCs) from oral squamous cell carcinoma (OSCC) patients presented cytotoxic CD8 T cell response against Streptococcus salivarius (S. salivarius), of which the frequency was positively associated with recurrence-free survival in OSCC patients. To identify the conditions required for regulating S. salivarius-specific CD8 T cell-mediated cytotoxicity, we selectively depleted individual components of the PBMCs, and observed that the depletion of monocytes/macrophages, but not other immune cell subsets, significantly downregulated the S...
March 9, 2018: Experimental Cell Research
Meng Tang, Bingji Liu, Xiaocui Bu, Peng Zhao
Tumor-associated macrophages (TAMs) contribute to tumor progression, but it is not clear how they are recruited to tumor sites. Here we showed that periostin (POSTN) was present at high levels in ovarian cancer ascetic fluids and was correlated with CD163+ TAMs. The high POSTN level and macrophage infiltration were inversely associated with relapse-free survival for ovarian cancer patients. In vitro studies showed that co-culture with macrophages significantly increased POSTN production in ovarian cancer cells...
March 12, 2018: Cancer Science
Brian A Aguado, Rachel M Hartfield, Grace G Bushnell, Joseph T Decker, Samira M Azarin, Dhaval Nanavati, Matthew J Schipma, Shreyas S Rao, Robert S Oakes, Yining Zhang, Jacqueline S Jeruss, Lonnie D Shea
Primary tumor (PT) immune cells and pre-metastatic niche (PMN) sites are critical to metastasis. Recently, synthetic biomaterial scaffolds used as PMN mimics are shown to capture both immune and metastatic tumor cells. Herein, studies are performed to investigate whether the scaffold-mediated redirection of immune and tumor cells would alter the primary tumor microenvironment (TME). Transcriptomic analysis of PT cells from scaffold-implanted and mock-surgery mice identifies differentially regulated pathways relevant to invasion and metastasis progression...
March 9, 2018: Advanced Healthcare Materials
Emanuele Giurisato, Qiuping Xu, Silvia Lonardi, Brian Telfer, Ilaria Russo, Adam Pearson, Katherine G Finegan, Wenbin Wang, Jinhua Wang, Nathanael S Gray, William Vermi, Zhengui Xia, Cathy Tournier
Owing to the prevalence of tumor-associated macrophages (TAMs) in cancer and their unique influence upon disease progression and malignancy, macrophage-targeted interventions have attracted notable attention in cancer immunotherapy. However, tractable targets to reduce TAM activities remain very few and far between because the signaling mechanisms underpinning protumor macrophage phenotypes are largely unknown. Here, we have investigated the role of the extracellular-regulated protein kinase 5 (ERK5) as a determinant of macrophage polarity...
March 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Xiaoli Tan, Shanqing Tao, Wenbo Liu, Antal Rockenbauer, Frederick A Villamena, Jay L Zweier, Yuguang Song, Yangping Liu
Electron paramagnetic resonance (EPR) spectroscopy coupled with the use of tetrathiatriarylmethyl (TAM) radicals has been a reliable method to detect superoxide radical (O2*-). However, the specificity and biocompatibility of TAM radicals need to be further improved. Although the derivatization may overcome the drawbacks of current TAM radicals, their esterification or amidation through the carboxylic groups greatly changes their redox properties and makes them inert to O2*-. Herein, we report the synthesis of a perthiatriarylmethyl (PST) radical and its dendritic derivatives PST-TA and PST-NA in which PST was covalently linked with the dendrons containing three and nine carboxylic acids (TA and NA), respectively...
March 5, 2018: Chemistry: a European Journal
Anupam Nath, Ramkrishna Pal, Leichombam Mohindro Singh, Himadri Saikia, Hasimur Rahaman, Sujit Kumar Ghosh, Ritwik Mazumder, Mahuya Sengupta
The tumor microenvironment, essentially hypoxic, is sustained by the hypoxia inducing factor (HIF), released from the pro-tumorigenic tumor associated macrophages (TAMs), functionally identical to the M2 phenotype macrophages. Stability of HIF mainly depends on molecular oxygen and an iron-dependent enzyme prolyl hydroxylase, while its activity may be inhibited by high levels of reactive oxygen species and nitric oxide. The present work showcases a novel approach utilizing the anti-tumorigenic potential of a gold-manganese oxide nanocomposite material in the tumor microenvironment that affects tumor hypoxia, exploring the possibility of restoring the immunoregulatory nature of TAMs from their pro-tumorigenic state...
February 27, 2018: International Immunopharmacology
Degao Chen, Jing Xie, Roland Fiskesund, Wenqian Dong, Xiaoyu Liang, Jiadi Lv, Xun Jin, Jinyan Liu, Siqi Mo, Tianzhen Zhang, Feiran Cheng, Yabo Zhou, Huafeng Zhang, Ke Tang, Jingwei Ma, Yuying Liu, Bo Huang
Resetting tumor-associated macrophages (TAMs) is a promising strategy to ameliorate the immunosuppressive tumor microenvironment and improve innate and adaptive antitumor immunity. Here we show that chloroquine (CQ), a proven anti-malarial drug, can function as an antitumor immune modulator that switches TAMs from M2 to tumor-killing M1 phenotype. Mechanistically, CQ increases macrophage lysosomal pH, causing Ca2+ release via the lysosomal Ca2+ channel mucolipin-1 (Mcoln1), which induces the activation of p38 and NF-κB, thus polarizing TAMs to M1 phenotype...
February 28, 2018: Nature Communications
Po-Hao Feng, Chih-Teng Yu, Kuan-Yuan Chen, Ching-Shan Luo, Shen Ming Wu, Chien-Ying Liu, Lu Wei Kuo, Yao-Fei Chan, Tzu-Tao Chen, Chih-Cheng Chang, Chun-Nin Lee, Hsiao-Chi Chuang, Chiou-Feng Lin, Chia-Li Han, Wei-Hwa Lee, Kang-Yun Lee
Background: Monocytic myeloid-derived suppressor cells (MDSCs), particularly the S100A9+ subset, has been shown initial clinical relevance. However, its role in EGFR-mutated lung adenocarcinoma, especially to EGFR-tyrosine kinase inhibitor (EGFR-TKI) is not clear. In a clinical setting of EGFR mutated lung adenocarcinoma, a role of the MDSC apart from T cell suppression was also investigated. Results: Blood monocytic S100A9+ MDSC counts were higher in lung cancer patients than healthy donors, and were associated with poor treatment response and shorter progression-free survival (PFS)...
January 26, 2018: Oncotarget
Sofia P Rebelo, Catarina Pinto, Tatiana R Martins, Nathalie Harrer, Marta F Estrada, Pablo Loza-Alvarez, José Cabeçadas, Paula M Alves, Emilio J Gualda, Wolfgang Sommergruber, Catarina Brito
The tumour microenvironment (TME) shapes disease progression and influences therapeutic response. Most aggressive solid tumours have high levels of myeloid cell infiltration, namely tumour associated macrophages (TAM). Recapitulation of the interaction between the different cellular players of the TME, along with the extracellular matrix (ECM), is critical for understanding the mechanisms underlying disease progression. This particularly holds true for prediction of therapeutic response(s) to standard therapies and interrogation of efficacy of TME-targeting agents...
May 2018: Biomaterials
Tomer Cooks, Ioannis S Pateras, Lisa M Jenkins, Keval M Patel, Ana I Robles, James Morris, Tim Forshew, Ettore Appella, Vassilis G Gorgoulis, Curtis C Harris
TP53 mutants (mutp53) are involved in the pathogenesis of most human cancers. Specific mutp53 proteins gain oncogenic functions (GOFs) distinct from the tumor suppressor activity of the wild-type protein. Tumor-associated macrophages (TAMs), a hallmark of solid tumors, are typically correlated with poor prognosis. Here, we report a non-cell-autonomous mechanism, whereby human mutp53 cancer cells reprogram macrophages to a tumor supportive and anti-inflammatory state. The colon cancer cells harboring GOF mutp53 selectively shed miR-1246-enriched exosomes...
February 22, 2018: Nature Communications
Xianmin Mu, Wei Shi, Yue Xu, Che Xu, Ting Zhao, Biao Geng, Jing Yang, Jinshun Pan, Shi Hu, Chen Zhang, Juan Zhang, Chao Wang, Jiajia Shen, Yin Che, Zheng Liu, Yuanfang Lv, Hao Wen, Qiang You
Tumor-associated macrophages (TAM) are prominent components of tumor microenvironment (TME) and capable of promoting cancer progression. However, the mechanisms for the formation of M2-like TAMs remain enigmatic. Here, we show that lactate is a pivotal oncometabolite in the TME that drives macrophage M2-polarization to promote breast cancer proliferation, migration, and angiogenesis. In addition, we identified that the activation of ERK/ STAT3, major signaling molecules in the lactate signaling pathway, deepens our molecular understanding of how lactate educates TAMs...
February 22, 2018: Cell Cycle
Jan Korbecki, Izabela Gutowska, Ireneusz Kojder, Dariusz Jeżewski, Marta Goschorska, Agnieszka Łukomska, Anna Lubkowska, Dariusz Chlubek, Irena Baranowska-Bosiacka
Recent years have seen considerable progress in understanding the biochemistry of cancer. For example, more significance is now assigned to the tumor microenvironment, especially with regard to intercellular signaling in the tumor niche which depends on many factors secreted by tumor cells. In addition, great progress has been made in understanding the influence of factors such as neurotensin, growth differentiation factor-15 (GDF-15), sphingosine-1-phosphate (S1P), and infection with cytomegalovirus (CMV) on the 'hallmarks of cancer' in glioblastoma multiforme...
January 23, 2018: Oncotarget
Jennifer Q Zhang, Shan Zeng, Gerardo A Vitiello, Adrian M Seifert, Benjamin D Medina, Michael J Beckman, Jennifer Loo, Juan Santamaria-Barria, Joanna H Maltbaek, Nesteene J Param, John A Moral, Julia N Zhao, Vinod Balachandran, Ferdinand Rossi, Cristina R Antonescu, Ronald P DeMatteo
Tyrosine kinase inhibition of gastrointestinal stromal tumors (GIST) is effective but typically culminates in resistance and is rarely curative. Immunotherapy has potential application to GIST, as we previously showed that T-cell checkpoint blockade increases the antitumor effects of imatinib. Here, we showed that ligation of CD40 using an agonistic antibody (anti-CD40) activated tumor-associated macrophages (TAMs) in vivo in a knock-in mouse model of GIST harboring a germline mutation in Kit exon 11. Activated TAMs had greater TNF production and NFkappaB signaling and directly inhibited tumor cells in vitro...
February 21, 2018: Cancer Immunology Research
Bengang Xing, Xiangzhao Ai, Ming Hu, Zhimin Wang, Linna Lyu, Wenmin Zhang, Jun Lin, Juan Li, Huang-Hao Yang
Near-infrared (NIR) light-mediated photodynamic therapy (PDT) especially based on lanthanide-doped upconversion nanocrystals (UCNs), have been extensively investigated as a promising strategy for effective cellular ablation owing to their unique optical properties to convert NIR light excitation into multiple short-wavelength emissions. Despite the deep tissue penetration of NIR light in living systems, the therapeutic efficiency is greatly restricted by insufficient oxygen supply in hypoxic tumor microenvironment...
February 21, 2018: Bioconjugate Chemistry
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