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https://www.readbyqxmd.com/read/29776993/tumor-immune-evasion-arises-through-loss-of-tnf-sensitivity
#1
Conor J Kearney, Stephin J Vervoort, Simon J Hogg, Kelly M Ramsbottom, Andrew J Freeman, Najoua Lalaoui, Lizzy Pijpers, Jessica Michie, Kristin K Brown, Deborah A Knight, Vivien Sutton, Paul A Beavis, Ilia Voskoboinik, Phil K Darcy, John Silke, Joseph A Trapani, Ricky W Johnstone, Jane Oliaro
Immunotherapy has revolutionized outcomes for cancer patients, but the mechanisms of resistance remain poorly defined. We used a series of whole-genome clustered regularly interspaced short palindromic repeat (CRISPR)-based screens performed in vitro and in vivo to identify mechanisms of tumor immune evasion from cytotoxic lymphocytes [CD8+ T cells and natural killer (NK) cells]. Deletion of key genes within the tumor necrosis factor (TNF) signaling, interferon-γ (IFN-γ) signaling, and antigen presentation pathways provided protection of tumor cells from CD8+ T cell-mediated killing and blunted antitumor immune responses in vivo...
May 18, 2018: Science Immunology
https://www.readbyqxmd.com/read/29771386/immunotherapy-in-cns-cancers-the-role-of-immune-cell-trafficking
#2
Nivedita M Ratnam, Mark R Gilbert, Amber J Giles
Glioblastoma (GBM) is a highly malignant CNS tumor with very poor survival despite intervention with conventional therapeutic strategies. Although the CNS is separated from the immune system by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), emerging evidence of immune surveillance and the selective infiltration of GBMs by immune suppressive cells indicates that there is breakdown or compromise of these physical barriers. This in turn offers hope that immunotherapy can be applied to specifically target and reduce tumor burden...
May 15, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29768737/providence-of-cd25-kir-cd127-foxp3-cd8-t-cell-subset-determines-the-dynamics-of-tumor-immune-surveillance
#3
Sreeparna Chakraborty, Pushpak Bhattacharjee, Abir K Panda, Kirti Kajal, Sayantan Bose, Gaurisankar Sa
CD8+ T-regulatory cells are progressively emerging as crucial components of immune system. The previous report suggests the presence of FOXP3-positive CD8+ Treg cells, similar to CD4+ Tregs, in cancer patients which produce high levels of IL10 and TGFβ for its immunosuppressive activities. At an early stage of tumor development, we have identified a subset of FOXP3-negative CD8+ CD25+ KIR+ CD127- a Treg-like subset which is essentially IFNγ-positive. However, this early induced CD8+ CD25+ CD127- T cell subset certainly distinct from the IFNγ+ CD8+ T-effecter cells...
May 16, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29760710/ionizing-radiation-induces-morphological-changes-and-immunological-modulation-of-jurkat-cells
#4
Patrick Voos, Sebastian Fuck, Fabian Weipert, Laura Babel, Dominique Tandl, Tobias Meckel, Stephanie Hehlgans, Claudia Fournier, Anna Moroni, Franz Rödel, Gerhard Thiel
Impairment or stimulation of the immune system by ionizing radiation (IR) impacts on immune surveillance of tumor cells and non-malignant cells and can either foster therapy response or side effects/toxicities of radiation therapy. For a better understanding of the mechanisms by which IR modulates T-cell activation and alters functional properties of these immune cells, we exposed human immortalized Jurkat cells and peripheral blood lymphocytes (PBL) to X-ray doses between 0.1 and 5 Gy. This resulted in cellular responses, which are typically observed also in naïve T-lymphocytes in response of T-cell receptor immune stimulation or mitogens...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29752311/myeloid-derived-suppressor-cells-impair-b-cell-responses-in-lung-cancer-through-il-7-and-stat5
#5
Yong Wang, Cara C Schafer, Kenneth P Hough, Sultan Tousif, Steven R Duncan, John F Kearney, Selvarangan Ponnazhagan, Hui-Chen Hsu, Jessy S Deshane
Myeloid-derived suppressor cells (MDSCs) are known suppressors of antitumor immunity, affecting amino acid metabolism and T cell function in the tumor microenvironment. However, it is unknown whether MDSCs regulate B cell responses during tumor progression. Using a syngeneic mouse model of lung cancer, we show reduction in percentages and absolute numbers of B cell subsets including pro-, pre-, and mature B cells in the bone marrow (BM) of tumor-bearing mice. The kinetics of this impaired B cell response correlated with the progressive infiltration of MDSCs...
May 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29751789/mechanisms-of-immune-evasion-in-breast-cancer
#6
Joshua P Bates, Roshanak Derakhshandeh, Laundette Jones, Tonya J Webb
Tumors develop multiple mechanisms of immune evasion as they progress, with some cancer types being inherently better at 'hiding' than others. With an increased understanding of tumor immune surveillance, immunotherapy has emerged as a promising treatment strategy for breast cancer, despite historically being thought of as an immunologically silent neoplasm. Some types of cancer, such as melanoma, bladder, and renal cell carcinoma, have demonstrated a durable response to immunotherapeutic intervention, however, breast neoplasms have not shown the same efficacy...
May 11, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29748897/myeloid-derived-suppressor-cells-mdscs-in-patients-with-solid-tumors-considerations-for-granulocyte-colony-stimulating-factor-treatment
#7
REVIEW
Katerina Pilatova, Beatrix Bencsikova, Regina Demlova, Dalibor Valik, Lenka Zdrazilova-Dubska
Myeloid-derived suppressor cells (MDSCs) have been shown to contribute to tumor escape from host immune surveillance and to cancer progression by production of tumor-promoting soluble factors. Granulocyte colony-stimulating factor (G-CSF) is a principle cytokine controlling granulocyte number. Recombinant human G-CSF (rhG-CSF) has become the main therapeutic agent for the treatment of neutropenia and prophylaxis of febrile neutropenia in cancer patients. However, we show here that rhG-CSF triggers accumulation of granulocytic and monocytic subsets...
May 10, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29745829/a-gene-profiling-deconvolution-approach-to-estimating-immune-cell-composition-from-complex-tissues
#8
Shu-Hwa Chen, Wen-Yu Kuo, Sheng-Yao Su, Wei-Chun Chung, Jen-Ming Ho, Henry Horng-Shing Lu, Chung-Yen Lin
BACKGROUND: A new emerged cancer treatment utilizes intrinsic immune surveillance mechanism that is silenced by those malicious cells. Hence, studies of tumor infiltrating lymphocyte populations (TILs) are key to the success of advanced treatments. In addition to laboratory methods such as immunohistochemistry and flow cytometry, in silico gene expression deconvolution methods are available for analyses of relative proportions of immune cell types. RESULTS: Herein, we used microarray data from the public domain to profile gene expression pattern of twenty-two immune cell types...
May 8, 2018: BMC Bioinformatics
https://www.readbyqxmd.com/read/29743205/preclinical-development-of-a-bispecific-antibody-that-safely-and-effectively-targets-cd19-and-cd47-for-the-treatment-of-b-cell-lymphoma-and-leukemia
#9
Vanessa Buatois, Zoë Johnson, Susana Salgado-Pires, Anne Papaïoannou, Eric Hatterer, Xavier Chauchet, Françoise Richard, Leticia Barba, Bruno Daubeuf, Laura Cons, Lucile Broyer, Matilde D'Asaro, Thomas Matthes, Simon LeGallou, Thierry Fest, Karin Tarte, Robert K Clarke Hinojosa, Eulàlia Genescà Ferrer, José María Ribera, Aditi Dey, Katharine Bailey, Adele K Fielding, Linda Eissenberg, Julie Ritchey, Michael Rettig, John F DiPersio, Marie H Kosco-Vilbois, Krzysztof Masternak, Nicolas Fischer, Limin Shang, Walter G Ferlin
CD47, a ubiquitously expressed innate immune checkpoint receptor that serves as a universal "don't eat me" signal of phagocytosis, is often up-regulated by hematological and solid cancers to evade immune surveillance. Development of CD47-targeted modalities is hindered by the ubiquitous expression of the target, often leading to rapid drug elimination and hemotoxicity including anemia. To overcome such liabilities, we have developed a fully human bispecific antibody, NI-1701, designed to co-engage CD47 and CD19 selectively on B cells...
May 9, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29721396/m7824-a-novel-bifunctional-anti-pd-l1-tgf%C3%AE-trap-fusion-protein-promotes-anti-tumor-efficacy-as-monotherapy-and-in-combination-with-vaccine
#10
Karin M Knudson, Kristin C Hicks, Xiaoling Luo, Jin-Qiu Chen, Jeffrey Schlom, Sofia R Gameiro
Tumors evade host immune surveillance through multiple mechanisms, including the generation of a tumor microenvironment that suppresses immune effector function. Secretion of TGFβ and upregulation of immune checkpoint programmed cell death ligand-1 (PD-L1) are two main contributors to immune evasion and tumor progression. Here, we examined the efficacy of a first-in-class bifunctional checkpoint inhibitor, the fusion protein M7824, comprising the extracellular domain of human TGFβRII (TGFβ Trap) linked to the C-terminus of human anti-PD-L1 heavy chain (αPD-L1)...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29710479/antigen-adjuvant-effects-of-icariin-in-enhancing-tumor-specific-immunity-in-mastocytoma-bearing-dba-2j-mice
#11
Xiaodi Zhang, Zhichen Kang, Qingjie Li, Jin Zhang, Sha Cheng, Hao Chang, Shanshan Wang, Shufang Cao, Tie Li, Jiawei Li, Yishan Wang, Yu Song, Hao Yu
Cancer immunotherapy has attracted much attention in recent years because of the ability of immune system to identify tumor cells and limit their growth. Icariin (ICA) is a natural flavonoid glucoside isolated from Epimedium plants and has shown a variety of pharmacological activities such as anti-inflammatory effects, immunological regulation and anticancer potency. Furthermore, it has immunoadjuvant effects on enhancing Th1-immune response, suggesting that ICA may serve as an adjuvant for cancer immunotherapy...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29710228/immune-profiling-of-premalignant-lesions-in-patients-with-lynch-syndrome
#12
Kyle Chang, Melissa W Taggart, Laura Reyes-Uribe, Ester Borras, Erick Riquelme, Reagan M Barnett, Guido Leoni, F Anthony San Lucas, Maria T Catanese, Federica Mori, Maria G Diodoro, Y Nancy You, Ernest T Hawk, Jason Roszik, Paul Scheet, Scott Kopetz, Alfredo Nicosia, Elisa Scarselli, Patrick M Lynch, Florencia McAllister, Eduardo Vilar
Importance: Colorectal carcinomas in patients with Lynch syndrome (LS) arise in a background of mismatch repair (MMR) deficiency, display a unique immune profile with upregulation of immune checkpoints, and response to immunotherapy. However, there is still a gap in understanding the pathogenesis of MMR-deficient colorectal premalignant lesions, which is essential for the development of novel preventive strategies for LS. Objective: To characterize the immune profile of premalignant lesions from a cohort of patients with LS...
April 16, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29703481/mechanisms-coupling-thrombin-to-metastasis-and-tumorigenesis
#13
Allison S Remiker, Joseph S Palumbo
The association of malignancy and thrombophilia is bidirectional, as evidenced by four decades of studies in animal models showing that hemostatic system components support cancer progression. Consistent with this view, clinical studies have suggested that anticoagulants not only limit thromboembolic complications associated with cancer, but also improve survival by impeding cancer progression, and may even prevent the development of cancer. In order to fully capitalize on this association, a detailed understanding of the mechanisms coupling hemostatic factors to cancer pathogenesis is required...
April 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29702007/dual-inhibition-of-stat1-and-stat3-activation-downregulates-expression-of-pd-l1-in-human-breast-cancer-cells
#14
Varun Sasidharan Nair, Salman M Toor, Bassam R Ali, Eyad Elkord
OBJECTIVES: Breast cancer is the most commonly diagnosed cancer, and it is a leading cause of cancer-related deaths in females worldwide. Triple-negative breast cancer (TNBC) constitutes 15% of breast cancer and shows distinct metastasis profiles with poor prognosis. Strong PD-L1 expression has been observed in some tumors, supporting their escape from immune surveillance. Targeting PD-L1 could be a promising therapeutic approach in breast cancer patients. We investigated potential molecular mechanisms for constitutive expression of PD-L1 by inhibiting upstream STAT1 and STAT3 signals...
April 27, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29692361/a-defect-in-kca3-1-channel-activity-limits-the-ability-of-cd8-t-cells-from-cancer-patients-to-infiltrate-an-adenosine-rich-microenvironment
#15
Ameet A Chimote, Andras Balajthy, Michael J Arnold, Hannah S Newton, Peter Hajdu, Julianne Qualtieri, Trisha Wise-Draper, Laura Conforti
The limited ability of cytotoxic T cells to infiltrate solid tumors hampers immune surveillance and the efficacy of immunotherapies in cancer. Adenosine accumulates in solid tumors and inhibits tumor-specific T cells. Adenosine inhibits T cell motility through the A2A receptor (A2A R) and suppression of KCa3.1 channels. We conducted three-dimensional chemotaxis experiments to elucidate the effect of adenosine on the migration of peripheral blood CD8+ T cells from head and neck squamous cell carcinoma (HNSCC) patients...
April 24, 2018: Science Signaling
https://www.readbyqxmd.com/read/29691234/drug-induced-senescent-multiple-myeloma-cells-elicit-nk-cell-proliferation-by-direct-or-exosome-mediated-il-15-trans-presentation
#16
Cristiana Borrelli, Biancamaria Ricci, Elisabetta Vulpis, Cinzia Fionda, Maria Rosaria Ricciardi, Maria Teresa Petrucci, Laura Masuelli, Agnese Peri, Marco Cippitelli, Alessandra Zingoni, Angela Santoni, Alessandra Soriani
Treatment of multiple myeloma (MM) cells with sub-lethal doses of genotoxic drugs leads to senescence and results in increased NK cell recognition and effector functions. Herein we demonstrated that doxorubicin- and melphalan-treated senescent cells display increased expression of IL15, a cytokine involved in NK cell activation, proliferation, and maturation. IL15 up-regulation was evident at the mRNA and protein level, both in MM cell lines and malignant plasma cells (PCs) from patients' bone marrow (BM) aspirates...
April 24, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29675003/role-of-micrornas-and-exosomes-in-helicobacter-pylori-and-epstein-barr-virus-associated-gastric-cancers
#17
REVIEW
Iva Polakovicova, Sofia Jerez, Ignacio A Wichmann, Alejandra Sandoval-Bórquez, Nicolás Carrasco-Véliz, Alejandro H Corvalán
Emerging evidence suggests that chronic inflammation caused by pathogen infection is connected to the development of various types of cancer. It is estimated that up to 20% of all cancer deaths is linked to infections and inflammation. In gastric cancer, such triggers can be infection of the gastric epithelium by either Helicobacter pylori ( H. pylori ), a bacterium present in half of the world population; or by Epstein-Barr virus (EBV), a double-stranded DNA virus which has recently been associated with gastric cancer...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29666300/a-pan-cancer-landscape-of-interactions-between-solid-tumors-and-infiltrating-immune-cell-populations
#18
David Tamborero, Carlota Rubio-Perez, Ferran Muiños, Radhakrishnan Sabarinathan, Josep Maria Piulats, Aura Muntasell, Rodrigo Dienstmann, Nuria Lopez-Bigas, Abel Gonzalez-Perez
PURPOSE: Throughout their development tumors are challenged by the immune system and they acquire features to evade its surveillance. A systematic view of these traits which sheds light on how tumors respond to immunotherapies is still lacking. EXPERIMENTAL DESIGN: Here, we computed the relative abundance of an array of immune cell populations to measure the immune infiltration pattern of 9,174 tumors of 29 solid cancers. We then clustered tumors with similar infiltration pattern to define immune-phenotypes...
April 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29658188/strategy-to-targeting-the-immune-resistance-and-novel-therapy-in-colorectal-cancer
#19
REVIEW
Wang Gang, Jun-Jie Wang, Rui Guan, Sun Yan, Feng Shi, Jia-Yan Zhang, Zi-Meng Li, Jing Gao, Xing-Li Fu
Assessing the CRC subtypes that can predict the outcome of colorectal cancer (CRC) in patients with immunogenicity seems to be a promising strategy to develop new drugs that target the antitumoral immune response. In particular, the disinhibition of the antitumoral T-cell response by immune checkpoint blockade has shown remarkable therapeutic promise for patients with mismatch repair (MMR) deficient CRC. In this review, the authors provide the update of the molecular features and immunogenicity of CRC, discuss the role of possible predictive biomarkers, illustrate the modern immunotherapeutic approaches, and introduce the most relevant ongoing preclinical study and clinical trials such as the use of the combination therapy with immunotherapy...
April 15, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29626519/polycomb-complex-protein-bmi1-confers-resistance-to-tamoxifen-in-estrogen-receptor-positive-breast-cancer
#20
Diane Ojo, Xiaozeng Lin, Ying Wu, Jessica Cockburn, Anita Bane, Damu Tang
We report that BMI1 promotes tamoxifen resistance in estrogen receptor (ER)-positive breast cancer (BC). BMI1 overexpression conferred MCF7 and TD47 cells resistance to tamoxifen; BMI1 knockdown sensitized the process. In MCF7-derived tamoxifen resistant cells, BMI1 expression was upregulated and BMI1 knockdown reduced the resistance. BMI1 is an oncogene; its oncogenic activity is attributed to BMI1-stimulated E3 ubiquitin ligase activity, a process that requires BMI1's ring finger (RF) domain. However, a BMI1 mutant without RF conferred tamoxifen resistance...
April 4, 2018: Cancer Letters
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