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https://www.readbyqxmd.com/read/28285690/the-cell-cell-interaction-between-tumor-associated-macrophages-and-small-cell-lung-cancer-cells-is-involved-in-tumor-progression-via-stat3-activation
#1
Toyohisa Iriki, Koji Ohnishi, Yukio Fujiwara, Hasita Horlad, Yoichi Saito, Cheng Pan, Koei Ikeda, Takeshi Mori, Makoto Suzuki, Hidenori Ichiyasu, Hirotsugu Kohrogi, Motohiro Takeya, Yoshihiro Komohara
OBJECTIVES: Small cell lung cancer (SCLC) is an aggressive tumor with a poor prognosis. It is well known that various stromal cells, including macrophages, play a role in tumor progression in several types of malignant tumors; however, the significance of tumor-associated macrophages (TAMs) in SCLC has not been fully elucidated. Signal transducer and activator of transcription 3 (STAT3) is a molecule well-known to be related to tumor progression. In the present study, we investigated the relationship of TAMs and SCLC cells to test the hypothesis that TAMs induce tumor progression in SCLC via STAT3 activation...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28258697/tim-3-and-its-role-in-regulating-anti-tumor-immunity
#2
REVIEW
Madhumita Das, Chen Zhu, Vijay K Kuchroo
Immunotherapy is being increasingly recognized as a key therapeutic modality to treat cancer and represents one of the most exciting treatments for the disease. Fighting cancer with immunotherapy has revolutionized treatment for some patients and therapies targeting the immune checkpoint molecules such as CTLA-4 and PD-1 have achieved durable responses in melanoma, renal cancer, Hodgkin's diseases and lung cancer. However, the success rate of these treatments has been low and a large number of cancers, including colorectal cancer remain largely refractory to CTLA-4 and PD-1 blockade...
March 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28256196/afatinib-ameliorates-osteoclast-differentiation-and-function-through-downregulation-of-rank-signaling-pathways
#3
Hye Jung Ihn, Ju Ang Kim, Yong Chul Bae, Hong-In Shin, Moon-Chang Baek, Eui Kyun Park
Non-small-cell lung cancer (NSCLC) is the third most common cancer that spreads to the bone, resulting in osteolytic lesions caused by hyperactivation of osteoclasts. Activating mutations in epidermal growth factor receptor-tyrosine kinase (EGF-TK) is frequently associated with NSCLC, and afatinib is a first-line therapeutic drug, irreversibly targeting EGF-TK. However, the effects of afatinib on osteoclast differentiation and activation as well as the underlying mechanism remain unclear. Afatinib dramatically suppressed receptor activator of nuclear factor κB (RANK) ligand (RANKL)-induced osteoclast formation in bone marrow macrophages (BMMs)...
March 3, 2017: BMB Reports
https://www.readbyqxmd.com/read/28254787/serine-proteases-enhance-immunogenic-antigen-presentation-on-lung-cancer-cells
#4
Haley L Peters, Satyendra C Tripathi, Celine Kerros, Hiroyuki Katayama, Haven R Garber, Lisa S St John, Lorenzo Federico, Ismail M Meraz, Jack A Roth, Boris Sepesi, Mourad Majidi, Kathryn Ruisaard, Karen Clise-Dwyer, Jason Roszik, Don L Gibbons, John Heymach, Stephen G Swisher, Chantale Bernantchez, Gheath Alatrash, Samir M Hanash, Jeffrey J Molldrem
Immunotherapies targeting immune checkpoints have proven efficacious in reducing the burden of lung cancer in patients; however, the antigenic targets of these re-invigorated T cells remain poorly defined. Lung cancer tumors contain tumor-associated macrophages (TAM) and neutrophils, which release the serine proteases neutrophil elastase (NE) and proteinase 3 (P3) into the tumor microenvironment. NE and P3 shape the antitumor adaptive immune response in breast cancer and melanoma. In this report, we demonstrate that lung cancer cells cross-presented the tumor-associated antigen PR1, derived from NE and P3...
March 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28245875/severe-nivolumab-induced-pneumonitis-preceding-durable-clinical-remission-in-a-patient-with-refractory-metastatic-lung-squamous-cell-cancer-a-case-report
#5
Hong Li, Weijie Ma, Ken Y Yoneda, Elizabeth H Moore, Yanhong Zhang, Lee L Q Pu, Garrett M Frampton, Michael Molmen, Philip J Stephens, Tianhong Li
BACKGROUND: Programmed cell death 1 (PD-1) and its ligand 1 (PD-L1) inhibitors have quickly become standard of care for patients with advanced non-small cell lung cancer and increasing numbers of other cancer types. In this report, we discuss the clinical history, pathological evaluation, and genomic findings in a patient with metastatic lung squamous cell cancer (SCC) who developed severe nivolumab-induced pneumonitis preceding durable clinical remission after three doses of nivolumab...
February 28, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28228217/-t-peptide-enhances-the-killing-effects-of-cisplatinum-on-lung-cancer
#6
Hongyi Zhang, Minghui Liu, Ying Li, Yongwen Li, Song Xu, Zhenhua Pan, Mingbiao Li, Haiyang Fan, Hongyu Liu, Jun Chen
BACKGROUND: T peptide is extensively used in anti-tumor treatment. The aims of this study were to investigate whether T peptide enhances cisplatinum efficiency while reducing its side effects and to identify its effective mechanisms. METHODS: (1) Human macrophage U937 cells were treated with T peptide and/or cisplatinum. The levels of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) of each group were detected by enzyme-linked immunosorbent assay (ELISA); (2) Xenograft mouse models of human lung cancer were treated with T peptide and/or cisplatinum once every five days for three times...
February 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28208020/graphene-oxide-induced-perturbation-to-plasma-membrane-and-cytoskeletal-meshwork-sensitize-cancer-cells-to-chemotherapeutic-agents
#7
Jianqiang Zhu, Ming Xu, Ming Gao, Zhihong Zhang, Yong Xu, Tian Xia, Sijin Liu
The outstanding physicochemical properties endow graphene materials (e.g., graphene oxide, GO) with beneficial potentials in diverse biomedical fields such as bioimaging, drug delivery, and biomolecular detection. GO recently emerged as a chemosensitizer; however, the detailed molecular basis underlying GO-conducted sensitization and corresponding biological effects are still elusive. Based on our recent findings that GO treatment at sublethal concentrations could impair the general cellular priming state, including disorders of plasma membrane and cytoskeleton construction, we aimed here to explore the mechanism of GO as a sensitizer to make cancer cells more susceptible to chemotherapeutic agents...
February 20, 2017: ACS Nano
https://www.readbyqxmd.com/read/28202524/scavenger-receptor-a1-prevents-metastasis-of-non-small-cell-lung-cancer-via-suppression-of-macrophage-serum-amyloid-a1
#8
Yan Zhang, Yongyue Wei, Bin Jiang, Lili Chen, Hui Bai, Xudong Zhu, Xiaoyu Li, Hanwen Zhang, Qing Yang, Junqing Ma, Yong Xu, Jingjing Ben, David C Christiani, Qi Chen
Mechanisms of crosstalk between tumor cells and tumor-associated macrophages (TAM) which drive metastasis are not fully understood. Scavenger receptor A1 (SR-A1) expressed primarily in macrophages has been associated with lung tumorigenesis. In this study, we used population genetics, transcriptomics and functional analyses to uncover how SR-A1 is involved in lung cancer and its prognosis. SR-A1 genetic variants were investigated for possible association with survival of advanced-stage NSCLC patients in the Harvard Lung Cancer Study cohort...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28197369/the-transcriptome-of-lung-tumor-infiltrating-dendritic-cells-reveals-a-tumor-supporting-phenotype-and-a-microrna-signature-with-negative-impact-on-clinical-outcome
#9
Lotte Pyfferoen, Elisabeth Brabants, Celine Everaert, Nancy De Cabooter, Kelly Heyns, Kim Deswarte, Manon Vanheerswynghels, Sofie De Prijck, Glenn Waegemans, Melissa Dullaers, Hamida Hammad, Olivier De Wever, Pieter Mestdagh, Jo Vandesompele, Bart N Lambrecht, Karim Y Vermaelen
Targeting immunomodulatory pathways has ushered a new era in lung cancer therapy. Further progress requires deeper insights into the biology of immune cells in the lung cancer micro-environment. Dendritic cells (DCs) represent a heterogeneous and highly plastic immune cell system with a central role in controlling immune responses. The intratumoral infiltration and activation status of DCs are emerging as clinically relevant parameters in lung cancer. In this study, we used an orthotopic preclinical model of lung cancer to dissect how the lung tumor micro-environment affects tissue-resident DCs and extract novel biologically and clinically relevant information...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28173772/potential-importance-of-protease-activated-receptor-par-1-expression-in-the-tumor-stroma-of-non-small-cell-lung-cancer
#10
Cong Lin, Christof J Majoor, Joris J T H Roelofs, Martijn D de Kruif, Hugo M Horlings, Keren Borensztajn, C Arnold Spek
BACKGROUND: Protease activated receptor (PAR)-1 expression is increased in a variety of tumor cells. In preclinical models, tumor cell PAR-1 appeared to be involved in the regulation of lung tumor growth and metastasis; however the role of PAR-1 in the lung tumor microenvironment, which is emerging as a key compartment in driving cancer progression, remained to be explored. METHODS: In the present study, PAR-1 gene expression was determined in lung tissue from patients with non-small-cell lung cancer (NSCLC) using a combination of publicly available RNA microarray datasets and in house-made tissue microarrays including tumor biopsies of 94 patients with NSCLC (40 cases of adenocarcinoma, 42 cases of squamous cell carcinoma and 12 cases of other type of NSCLC at different stages)...
February 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28166195/detecting-intratumoral-heterogeneity-of-egfr-activity-by-liposome-based-in-vivo-transfection-of-a-fluorescent-biosensor
#11
G Weitsman, N J Mitchell, R Evans, A Cheung, T L Kalber, R Bofinger, G O Fruhwirth, M Keppler, Z V F Wright, P R Barber, P Gordon, T de Koning, W Wulaningsih, K Sander, B Vojnovic, S Ameer-Beg, M Lythgoe, J N Arnold, E Årstad, F Festy, H C Hailes, A B Tabor, T Ng
Despite decades of research in the epidermal growth factor receptor (EGFR) signalling field, and many targeted anti-cancer drugs that have been tested clinically, the success rate for these agents in the clinic is low, particularly in terms of the improvement of overall survival. Intratumoral heterogeneity is proposed as a major mechanism underlying treatment failure of these molecule-targeted agents. Here we highlight the application of fluorescence lifetime microscopy (FLIM)-based biosensing to demonstrate intratumoral heterogeneity of EGFR activity...
February 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28160492/a-prognostic-4-gene-expression-signature-for-squamous-cell-lung-carcinoma
#12
Jun Li, Jing Wang, Yanbin Chen, Lijie Yang, Sheng Chen
Squamous cell lung carcinoma (SQCLC), a common and fatal subtype of lung cancer, caused lots of mortalities and showed different outcomes in prognosis. This study was to screen key genes and to figure a prognostic signature to cluster the patients with SQCLC. RNA-Seq data from 550 patients with SQCLC were downloaded from The Cancer Genome Atlas (TCGA). Genetically changed genes were identified and analyzed in univariate survival analysis. Genes significantly influencing prognosis were selected with frequency higher than 100 in lasso regression...
February 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28147282/sr-b1-is-a-silica-receptor-that-mediates-canonical-inflammasome-activation
#13
Misato Tsugita, Nobuyuki Morimoto, Manabu Tashiro, Kengo Kinoshita, Masafumi Nakayama
The inhalation of silica dust is associated with fibrosis and lung cancer, which are triggered by macrophage inflammatory responses; however, how macrophages recognize silica remains largely unknown. Here, we identify by functional expression cloning the class B scavenger receptor SR-B1 as a silica receptor. Through an extracellular α-helix, both mouse and human SR-B1 specifically recognized amorphous and crystalline silica, but not titanium dioxide nanoparticles, latex nanoparticles, or monosodium urate crystals, although all particles exhibited negative surface potentials...
January 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/28121002/immune-enhancement-effects-and-extraction-optimization-of-polysaccharides-from-citrus-aurantium-l-var-amara-engl
#14
Chun-Yan Shen, Li Yang, Jian-Guo Jiang, Chao-Yang Zheng, Wei Zhu
The crude polysaccharides of Citrus aurantium L. var. amara Engl (CAVAPs) were extracted and their bioactivities including DPPH radical scavenging activity, cytotoxicity to human breast cancer cells, MCF-7, as well as lung cancer cells, HCC827, and their immune-enhancement activity were evaluated. Results showed that CAVAPs exhibited better immunoenhancement activity compared to the DPPH radical scavenging and anticancer activities. Subsequently, the immune enhancement activity of CAVAPs on RAW264.7 cells was further observed and the results displayed that CAVAPs could significantly stimulate the production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in RAW264...
January 25, 2017: Food & Function
https://www.readbyqxmd.com/read/28119812/inhalable-oridonin-loaded-poly-lactic-co-glycolic-acid-large-porous-microparticles-for-in-situ-treatment-of-primary-non-small-cell-lung-cancer
#15
Lifei Zhu, Miao Li, Xiaoyan Liu, Lina Du, Yiguang Jin
Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. Traditional chemotherapy for this disease leads to serious side effects. Here we prepared an inhalable oridonin-loaded poly(lactic-co-glycolic)acid (PLGA) large porous microparticle (LPMP) for in situ treatment of NSCLC with the emulsion/solvent evaporation/freeze-drying method. The LPMPs were smooth spheres with many internal pores. Despite a geometric diameter of ~10 µm, the aerodynamic diameter of the spheres was only 2.72 µm, leading to highly efficient lung deposition...
January 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28108629/myeloid-stat3-promotes-lung-tumorigenesis-by-transforming-tumor-immunosurveillance-into-tumor-promoting-inflammation
#16
Jingjiao Zhou, Zhaoxia Qu, Fan Sun, Lei Han, Liwen Li, Shapei Yan, Laura P Stabile, Lin-Feng Chen, Jill M Siegfried, Gutian Xiao
One of the most fundamental and challenging questions in the cancer field is how immunity in patients with cancer is transformed from tumor immunosurveillance to tumor-promoting inflammation. Here, we identify the transcription factor STAT3 as the culprit responsible for this pathogenic event in lung cancer development. We found that antitumor type 1 CD4(+) T-helper (Th1) cells and CD8(+) T cells were directly counter balanced in lung cancer development with tumor-promoting myeloid-derived suppressor cells (MDSCs) and suppressive macrophages, and that activation of STAT3 in MDSCs and macrophages promoted tumorigenesis through pulmonary recruitment and increased resistance of suppressive cells to CD8(+) T cells, enhancement of cytotoxicity toward CD4(+) and CD8(+) T cells, induction of regulatory T cell (Treg), inhibition of dendritic cells (DC), and polarization of macrophages toward the M2 phenotype...
March 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28103926/clinical-significance-of-soluble-cd163-in-polymyositis-related-or-dermatomyositis-related-interstitial-lung-disease
#17
Yasunori Enomoto, Yuzo Suzuki, Hironao Hozumi, Kazutaka Mori, Masato Kono, Masato Karayama, Kazuki Furuhashi, Tomoyuki Fujisawa, Noriyuki Enomoto, Yutaro Nakamura, Naoki Inui, Daisuke Suzuki, Noriyoshi Ogawa, Ran Nakashima, Tsuneyo Mimori, Toshihide Iwashita, Takafumi Suda
BACKGROUND: Macrophage activation is involved in the pathogenesis of polymyositis (PM)/dermatomyositis (DM). CD163, a scavenger receptor expressed on the surface of activated macrophages, mediates anti-inflammatory functions. This study aimed to evaluate the clinical significance of soluble CD163 (sCD163) in PM/DM-related interstitial lung disease (ILD). METHODS: The main subjects were 48 patients with PM/DM-related ILD. As controls, 10 patients with PM/DM without ILD and 20 healthy volunteers were enrolled...
January 19, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28101568/puerarin-inhibits-m2-polarization-and-metastasis-of-tumor-associated-macrophages-from-nsclc-xenograft-model-via-inactivating-mek-erk-1-2-pathway
#18
Honggang Kang, Jing Zhang, Baozhong Wang, Meirong Liu, Jun Zhao, Mengxiang Yang, Yingxue Li
Non-small cell lung carcinoma (NSCLC) metastasis is responsible for most of cancer-related mortality. The tumor associated macrophages (TAMs) are known to be crucial cells in lung cancer and are usually divided into two antagonistic types, M1 and M2. Puerarin has a wide spectrum of pharmacological properties. The present study explores puerarin on macrophage polarization and metastasis of NSCLC. The results demonstrated that puerarin inhibited tumor growth and tumor volumes in NSCLC xenograft model, increased M1 markers [CD197+, inducible nitric oxide synthase (iNOS)+, CD40+)] and reduced M2 markers (CD206+, Arg-1+ and CD163+)...
February 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28101225/monocytic-myeloid-derived-suppressor-cells-as-a-potent-suppressor-of-tumor-immunity-in-non-small-cell-lung-cancer
#19
Katarzyna Pogoda, Maria Pyszniak, Paweł Rybojad, Jacek Tabarkiewicz
Immunotherapy is a promising therapeutic option for patients with non-small cell lung cancer (NSCLC) who do not qualify for surgery. In patients with advanced NSCLC, systemic immune suppression is frequently observed, therefore, researchers are investigating the tumor microenvironment for less invasive and more effective methods of treating lung cancer. Monocytic myeloid-derived suppressor cells (Mo-MDSCs) are potent suppressors of tumor immunity; therefore, this population may significantly impede the application of immunotherapy to treat cancer...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28061450/th1high-in-tumor-microenvironment-is-an-indicator-of-poor-prognosis-for-patients-with-nsclc
#20
Huang Jian, Shen Fangrong, Huang Haitao, Ling Chunhua, Zhang Guangbo
CD4+Th subsets play an important role in tumor progression but their expression characteristics and clinical significance in human tumor microenvironment remains unclear. In this study, we aim to analyze the expression and clinical significance of tissue-infiltrating Th1, Th2 and Th17 in lung cancer by flow cytometry. We found that the frequency of CD3+CD4+IFN-γ+Th1 in tumor nest was significantly lower than that in tumor boundary, adjacent normal lung tissue or corresponding lymph node tissue; the frequency of CD3+CD4+IL-4+Th2 in tumor nest was significantly higher than that in tumor boundary, adjacent normal lung tissue or corresponding lymph node tissue; the frequency of CD3+CD4+IL-17+Th17 in tumor nest was significantly lower than that in tumor boundary, but not adjacent normal tissue or corresponding lymph node tissue...
January 3, 2017: Oncotarget
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