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https://www.readbyqxmd.com/read/27866850/deubiquitination-and-stabilization-of-pd-l1-by-csn5
#1
Seung-Oe Lim, Chia-Wei Li, Weiya Xia, Jong-Ho Cha, Li-Chuan Chan, Yun Wu, Shih-Shin Chang, Wan-Chi Lin, Jung-Mao Hsu, Yi-Hsin Hsu, Taewan Kim, Wei-Chao Chang, Jennifer L Hsu, Hirohito Yamaguchi, Qingqing Ding, Yan Wang, Yi Yang, Chung-Hsuan Chen, Aysegul A Sahin, Dihua Yu, Gabriel N Hortobagyi, Mien-Chie Hung
Pro-inflammatory cytokines produced in the tumor microenvironment lead to eradication of anti-tumor immunity and enhanced tumor cell survival. In the current study, we identified tumor necrosis factor alpha (TNF-α) as a major factor triggering cancer cell immunosuppression against T cell surveillance via stabilization of programmed cell death-ligand 1 (PD-L1). We demonstrated that COP9 signalosome 5 (CSN5), induced by NF-κB p65, is required for TNF-α-mediated PD-L1 stabilization in cancer cells. CSN5 inhibits the ubiquitination and degradation of PD-L1...
November 14, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27862100/role-of-epigenetic-modification-and-immunomodulation-in-a-murine-prostate-cancer-model
#2
Jay E Sulek, Samuel P Robinson, Albert A Petrossian, Shaoqing Zhou, Ekaterine Goliadze, Masoud H Manjili, Amir Toor, Georgi Guruli
INTRODUCTION: Decreased expression of highly immunogenic cancer-testis antigens (CTA) might help tumor to achieve low immunogenicity, escape immune surveillance and grow unimpeded. Our aim was to evaluate CTA expression in tumor and normal tissues and to investigate possible means of improving the immune response in a murine prostate cancer (CaP) model by using the combination of epigenetic modifier 5-azacitidine (5-AzaC) and immunomodulator lenalidomide. No study to date has examined the effect of this combination on the prostate cancer or its impact on antigen-presenting cells (APC)...
November 8, 2016: Prostate
https://www.readbyqxmd.com/read/27857157/inhibiting-mdsc-differentiation-from-bone-marrow-with-phytochemical-polyacetylenes-drastically-impairs-tumor-metastasis
#3
Wen-Chi Wei, Sheng-Yen Lin, Chun-Wen Lan, Yu-Chen Huang, Chih-Yu Lin, Pei-Wen Hsiao, Yet-Ran Chen, Wen-Chin Yang, Ning-Sun Yang
Myeloid-derived suppressor cells (MDSCs) are implicated in the promotion of tumor metastasis by protecting metastatic cancerous cells from immune surveillance and have thus been suggested as novel targets for cancer therapy. We demonstrate here that oral feeding with polyacetylenic glycosides (BP-E-F1) from the medicinal plant Bidens pilosa effectively suppresses tumor metastasis and inhibits tumor-induced accumulation of granulocytic (g) MDSCs, but does not result in body weight loss in a mouse mammary tumor-resection model...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27856600/tti-621-sirp%C3%AE-fc-a-cd47-blocking-innate-immune-checkpoint-inhibitor-with-broad-anti-tumor-activity-and-minimal-erythrocyte-binding
#4
Penka S Petrova, Natasja N Viller, Mark Wong, Xinli Pang, Gloria H Y Lin, Karen Dodge, Vien Chai, Hui Chen, Vivian Lee, Violetta House, Noel T Vigo, Debbie Jin, Tapfuma Mutukura, Marilyse Charbonneau, Tran Truong, Stéphane Viau, Lisa D Johnson, Emma Linderoth, Eric L Sievers, Saman Maleki Vareki, Rene Figueredo, Macarena Pampillo, James Koropatnick, Suzanne Trudel, Nathan Mbong, Liqing Jin, Jean C Y Wang, Robert A Uger
PURPOSE: The ubiquitously expressed transmembrane glycoprotein CD47 delivers an anti-phagocytic (do-not-eat) signal by binding signal-regulatory protein α (SIRPα) on macrophages. CD47 is over-expressed in cancer cells and its expression is associated with poor clinical outcomes. TTI 621 (SIRPαFc) is a fully human recombinant fusion protein that blocks the CD47:SIRPα-axis by binding to human CD47 and enhancing phagocytosis of malignant cells. Blockade of this inhibitory axis using TTI-621 has emerged as a promising therapeutic strategy to promote tumor cell eradication...
November 17, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27855694/cd274-promotes-cell-cycle-entry-of-leukemia-initiating-cells-through-jnk-cyclin-d2-signaling
#5
Xia Fang, Chiqi Chen, Fangzhen Xia, Zhuo Yu, Yaping Zhang, Feifei Zhang, Hao Gu, Jiangbo Wan, Xiaocui Zhang, Wei Weng, Cheng Cheng Zhang, Guo-Qiang Chen, Aibing Liang, Li Xie, Junke Zheng
BACKGROUND: CD274 (programmed death ligand 1, also known as B7H1) is expressed in both solid tumors and hematologic malignancies and is of critical importance for the escape of tumor cells from immune surveillance by inhibiting T cell function via its receptor, programmed death 1 (PD-1). Increasing evidence indicates that functional monoclonal antibodies of CD274 may potently enhance the antitumor effect in many cancers. However, the role of CD274 in leukemia-initiating cells (LICs) remains largely unknown...
November 17, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27854240/the-impact-of-chemotherapy-radiation-and-epigenetic-modifiers-in-cancer-cell-expression-of-immune-inhibitory-and-stimulatory-molecules-and-anti-tumor-efficacy
#6
REVIEW
Jessica Ann Chacon, Keith Schutsky, Daniel J Powell
Genomic destabilizers, such as radiation and chemotherapy, and epigenetic modifiers are used for the treatment of cancer due to their apoptotic effects on the aberrant cells. However, these therapies may also induce widespread changes within the immune system and cancer cells, which may enable tumors to avoid immune surveillance and escape from host anti-tumor immunity. Genomic destabilizers can induce immunogenic death of tumor cells, but also induce upregulation of immune inhibitory ligands on drug-resistant cells, resulting in tumor progression...
November 14, 2016: Vaccines
https://www.readbyqxmd.com/read/27852037/placental-immune-editing-switch-pies-learning-about-immunomodulatory-pathways-from-a-unique-case-report
#7
Miguel H Bronchud, Francesc Tresserra, Wenjie Xu, Sarah Warren, Maite Cusido, Bernat Zantop, Ana Claudia Zenclussen, Alessandra Cesano
The hypothesis of this work is that, in order to escape the natural immune surveillance mechanisms, cancer cells and the surrounding microenvironment might express ectopically genes that are physiologically present in the placenta to mediate fetal immune-tolerance. These natural "placental immune-editing switch" mechanisms (PIES) may represent the result of millions of years of mammalian evolution developed to allow materno-fetal tolerance. Here, we introduce genes of the immune regulatory pathways that are either similarly over- or under-expressed in tumor vs normal tissue...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27843441/the-janus-face-of-death-receptor-signaling-during-tumor-immunoediting
#8
REVIEW
Eimear O' Reilly, Andrea Tirincsi, Susan E Logue, Eva Szegezdi
Cancer immune surveillance is essential for the inhibition of carcinogenesis. Malignantly transformed cells can be recognized by both the innate and adaptive immune systems through different mechanisms. Immune effector cells induce extrinsic cell death in the identified tumor cells by expressing death ligand cytokines of the tumor necrosis factor ligand family. However, some tumor cells can escape immune elimination and progress. Acquisition of resistance to the death ligand-induced apoptotic pathway can be obtained through cleavage of effector cell expressed death ligands into a poorly active form, mutations or silencing of the death receptors, or overexpression of decoy receptors and pro-survival proteins...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27835902/squamous-cell-carcinomas-escape-immune-surveillance-via-inducing-chronic-activation-and-exhaustion-of-cd8-t-cells-co-expressing-pd-1-and-lag-3-inhibitory-receptors
#9
Ameet K Mishra, Tanya Kadoishi, Xiaoguang Wang, Emily Driver, Zhangguo Chen, Xiao-Jing Wang, Jing H Wang
Squamous cell carcinoma (SCC) is the second commonest type of skin cancer. Moreover, about 90% of head and neck cancers are SCCs. SCCs develop at a significantly higher rate under chronic immunosuppressive conditions, implicating a role of immune surveillance in controlling SCCs. It remains largely unknown how SCCs evade immune recognition. Here, we established a mouse model by injecting tumor cells derived from primary SCCs harboring KrasG12D mutation and Smad4 deletion into wild-type (wt) or CD8-/- recipients...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27829133/lactate-wreaks-havoc-on-tumor-infiltrating-t-and-nk-cells
#10
Kristen E N Scott, John L Cleveland
Both cancer cells and activated T and NK immune cells display enhanced nutrient uptake and metabolism characteristic of the Warburg phenotype. In this issue of Cell Metabolism, Brand et al. (2016) demonstrate that cancer cell LDHA-derived lactic acid selectively disables T and NK cell activation and tumor immune surveillance.
November 8, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27823972/%C3%AE-%C3%AE-t-cells-in-cancer-immunotherapy
#11
REVIEW
Chang Zou, Pan Zhao, Zhangang Xiao, Xianghua Han, Fan Fu, Li Fu
γδ T cells are one of the three immune cell types that express antigen receptors. They contribute to lymphoid antitumor surveillance and bridge the gap between innate and adaptive immunity. γδ T cells have the capacity of secreting abundant cytokines and exerting potent cytotoxicity against a wide range of cancer cells. γδ T cells exhibit important roles in immune-surveillance and immune defense against tumors and have become attractive effector cells for cancer immunotherapy. γδ T cells mediate anti-tumor therapy mainly by secreting pro-apoptotic molecules and inflammatory cytokines, or through a TCR-dependent pathway...
November 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27816403/a-review-of-the-pd-1-pd-l1-checkpoint-in-bladder-cancer-from-mediator-of-immune-escape-to-target-for-treatment
#12
REVIEW
Tian C Zhou, Alexander I Sankin, Steven A Porcelli, David S Perlin, Mark P Schoenberg, Xingxing Zang
PURPOSE: Recent observations have focused attention on the means that human tumors employ to evade host defense systems critical to immune surveillance. The concepts of immunotherapy are familiar to urologists because of the use of bacillus Calmette-Guérin in bladder cancer. Research demonstrating the importance of checkpoint inhibitors in suppressing immune responses against tumors has heightened interest in immunotherapy at a time when there is a need for alternatives to bacillus Calmette-Guérin...
November 2, 2016: Urologic Oncology
https://www.readbyqxmd.com/read/27815390/kv1-3-channels-mark-functionally-competent-cd8-tumor-infiltrating-lymphocytes-in-head-and-neck-cancer
#13
Ameet A Chimote, Peter Hajdu, Alexandros M Sfyris, Brittany N Gleich, Trisha Wise-Draper, Keith A Casper, Laura Conforti
Tumor infiltrating lymphocytes (TIL) are potent mediators of an anti-tumor response. However, their function is attenuated in solid tumors. CD8(+) T cell effector functions such as cytokine and granzyme production depend on cytoplasmic Ca(2+), which is controlled by ion channels. In particular, Kv1.3 channels regulate the membrane potential and Ca(2+) influx in human effector memory T (TEM) cells. In this study, we assessed the contribution of reduced Kv1.3 and Ca(2+) flux on TIL effector function in head and neck cancer (HNC)...
November 4, 2016: Cancer Research
https://www.readbyqxmd.com/read/27803740/antagonizing-programmed-death-1-and-programmed-death-ligand-1-as-a-therapeutic-approach-for-gastric-cancer
#14
REVIEW
Xiaojun Liu, Zhongxia Yang, Olivier Latchoumanin, Liang Qiao
Malignant tumor cells are equipped with mechanisms that can help them escape the surveillance by host immune system. Immune checkpoint molecules can transduce coinhibitory signals to immunocompetent cells and exert immunosuppressive roles in antitumor immunity. Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) are the two important checkpoint molecules with great potential in targeted cancer therapy. Several antibodies targeting PD-1 and PD-L1 have been approved for clinical use. In this review, we focus on the recent development of targeting PD-1 and PD-L1 in gastric cancer (GC) therapy...
November 2016: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/27796822/effects-of-shugan-jianpi-formula-on-myeloid-derived-suppression-cells-mediated-depression-breast-cancer-mice
#15
Yu-Tong Lu, Jie Li, Xin Qi, Ying-Xia Pei, Wen-Guang Shi, Hong-Sheng Lin
OBJECTIVE: To observe the intervention effect of Shugan Jianpi Formula (, SGJPF) on a breast cancer mouse model with depression and investigate the underlying mechanism of SGJPF in preventing the development of breast cancer. METHODS: The breast cancer model was induced by inoculation of breast cancer cells, the depression model was induced by chronic stress stimuli, and the depression cancer model was established by combining the two factors. The mice were divided into 7 groups: normal control, depression model, tumor model, depression tumor model, SGJPF, chemotherapy, and SGJPF+chemotherapy groups...
October 28, 2016: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/27794498/phytomedicine-modulating-oxidative-stress-and-the-tumor-microenvironment-for-cancer-therapy
#16
REVIEW
Yu-Ting Cheng, Chun-Chih Yang, Lie-Fen Shyur
In spite of the current advances and achievements in systems biology and translational medicinal research, the current strategies for cancer therapy, such as radiotherapy, targeted therapy, immunotherapy and chemotherapy remain palliative or unsatisfactory due to tumor metastasis or recurrence after surgery/therapy, drug resistance, adverse side effects, and so on. Oxidative stress (OS) plays a critical role in chronic/acute inflammation, carcinogenesis, tumor progression, and tumor invasion/metastasis which is also attributed to the dynamic and complex properties and activities in the tumor microenvironment (TME)...
October 26, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27771887/macrophage-migration-inhibitory-factor-mif-biological-activities-and-relation-with-cancer
#17
Camila Cristina Guimarães Nobre, Josélio Maria Galvão de Araújo, Thales Allyrio Araújo de Medeiros Fernandes, Ricardo Ney Oliveira Cobucci, Daniel Carlos Ferreira Lanza, Vânia Sousa Andrade, José Veríssimo Fernandes
Macrophage migration inhibitory factor (MIF) emerged in recent years as an important inflammation mediator, playing a prominent role in the pathogenesis of various types of malignant neoplasm. MIF is a glycoprotein that presents a wide spectrum of biological activities and exerts a complex interaction with various cellular signaling pathways, causing imbalance of homeostasis. Experimental and clinical studies show that high levels of MIF are found in almost all types of human cancers and are implicated in seemingly all stages of development of the tumors...
October 23, 2016: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/27764780/the-concept-of-immune-surveillance-against-tumors-the-first-theories
#18
Domenico Ribatti
The immune system plays a major role in the surveillance against tumors. To avoid attack from the immune system, tumor cells develop different strategies to escape immune surveillance. Evidence of immune surveillance comes from both animal models and clinical observations. Mice with a wide variety of immunodeficiencies have a high rate of tumor incidence and are more susceptible to transplanted or chemical carcinogen-induced tumors. Immunosuppressed patients have a high incidence of tumors. However, many patients develop cancer even in the presence of an apparently normal immune system...
October 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27760559/impact-of-aging-on-host-immune-response-and-survival-in-melanoma-an-analysis-of-3-patient-cohorts
#19
Sarah A Weiss, Joseph Han, Farbod Darvishian, Jeremy Tchack, Sung Won Han, Karolina Malecek, Michelle Krogsgaard, Iman Osman, Judy Zhong
BACKGROUND: Age has been reported as an independent prognostic factor for melanoma-specific survival (MSS). We tested the hypothesis that age impacts the host anti-tumor immune response, accounting for age-specific survival outcomes in three unique melanoma patient cohorts. METHODS: We queried the U.S. population-based Surveillance, Epidemiology, and End Results Program (SEER), the prospective tertiary care hospital-based Interdisciplinary Melanoma Cooperative Group (IMCG) biorepository, and the Cancer Genome Atlas (TCGA) biospecimen database to test the association of patient age at time of melanoma diagnosis with clinicopathologic features and survival outcomes...
October 19, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27756426/exosomes-in-tumor-microenvironment-novel-transporters-and-biomarkers
#20
Zhen Wang, Jun-Qiang Chen, Jin-Lu Liu, Lei Tian
Tumor microenvironment (TME) plays an integral part in the biology of cancer, participating in tumor initiation, progression, and response to therapy. Exosome is an important part of TME. Exosomes are small vesicles formed in vesicular bodies with a diameter of 30-100 nm and a classic "cup" or "dish" morphology. They can contain microRNAs, mRNAs, DNA fragments and proteins, which are shuttled from a donor cell to recipient cells. Exosomes secreted from tumor cells are called tumor-derived (TD) exosomes. There is emerging evidence that TD exosomes can construct a fertile environment to support tumor proliferation, angiogenesis, invasion and premetastatic niche preparation...
October 19, 2016: Journal of Translational Medicine
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