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https://www.readbyqxmd.com/read/28527911/cancer-stem-cells-at-the-forefront-of-personalized-medicine-and-immunotherapy
#1
REVIEW
Micol E Fiori, Lidia Villanova, Ruggero De Maria
Cancer stem cells (CSCs) represent the main target of the current efforts to eradicate cancer, because of their ability to promote metastatic dissemination and survive cytotoxic therapies. Here, we highlight the potential of patient-derived CSCs as an in vitro and in vivo pre-clinical model and of liquid biopsy as a diagnostic, prognostic and predictive tool. We discuss recently developed therapeutic strategies aiming at specifically targeting the cancer stem cell population, particularly focusing on the latest advances in cancer immunotherapy...
May 18, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28522598/immunotherapeutic-approaches-of-il-1-neutralization-in-the-tumor-microenvironment
#2
REVIEW
Ron N Apte, Elena Voronov
IL-1 is a pleiotropic cytokine that controls inflammation, immunity, and hemopoiesis. The major IL-1 agonistic molecules are IL-1α and IL-1β, which bind to IL-1R type I (IL-1R1) and induce similar biologic functions. The IL-1R antagonist (IL-1Ra) is a physiologic inhibitor of IL-1R1 signaling. In the tumor microenvironment, IL-1 is expressed by malignant, stromal, and infiltrating cells and supports tumor invasiveness and progression. We have shown that in the tumor microenvironment, the IL-1 agonistic molecules act different as a result of their local amounts and their compartmentalization within the producing cells...
May 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28521455/kdm3a-promotes-inhibitory-cytokines-secretion-by-participating-in-tlr4-regulation-of-foxp3-transcription-in-lung-adenocarcinoma-cells
#3
Yinan Li, Wei Yang, Bin Wu, Yaqing Liu, Dongbei Li, Yantong Guo, Haiying Fu, Yi Li
Toll-like receptor 4 (TLR4) is a pattern recognition receptors, a member of the Toll-like receptor family and it serves a role in innate and acquired immunity. It has previously been reported that TLR4 was overexpressed in a variety of tumor tissues and cells, including colorectal cancer, gastric cancer and ovarian cancer. In the tumor microenvironment, the TLR4 signaling pathway may be activated in order to upregulate forkhead box P3 (Foxp3) expression in regulatory T cells (Tregs), and thus enhance the immunosuppressive function of Tregs...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521292/tumor-infiltrating-immune-cells-and-prognosis-in-gastric-cancer-a-systematic-review-and-meta-analysis
#4
Wen Jiang, Ke Liu, Qing Guo, Ji Cheng, Liming Shen, Yinghao Cao, Jing Wu, Jianguo Shi, Heng Cao, Bo Liu, Kaixiong Tao, Guobin Wang, Kailin Cai
Tumor-infiltrating immune cells are a pivotal component of the tumor microenvironment (TME), but their indicative role remains poorly defined. A meta-analysis was performed to reveal the prognostic efficiency of tumor-infiltrating immune cells in gastric cancer (GC). By searching PubMed and Embase, we identified a total of 35 eligible articles that involved 4888 patients. Random or fixed effect models were employed to extract pooled hazard ratios (HRs) with 95% confidence intervals (CIs). Our results indicated that high CD3+ lymphocyte infiltration in all the locations (AG), the tumor nest (TN), and the tumor stroma (TS) predicted better overall survival (OS) (HR=0...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28516983/nanoparticle-design-strategies-for-enhanced-anticancer-therapy-by-exploiting-the-tumour-microenvironment
#5
REVIEW
Yunlu Dai, Can Xu, Xiaolian Sun, Xiaoyuan Chen
Nanovehicles can efficiently carry and deliver anticancer agents to tumour sites. Compared with normal tissue, the tumour microenvironment has some unique properties, such as vascular abnormalities, hypoxia and acidic pH. There are many types of cells, including tumour cells, macrophages, immune and fibroblast cells, fed by defective blood vessels in the solid tumour. Exploiting the tumour microenvironment can benefit the design of nanoparticles for enhanced therapeutic effectiveness. In this review article, we summarized the recent progress in various nanoformulations for cancer therapy, with a special emphasis on tumour microenvironment stimuli-responsive ones...
May 18, 2017: Chemical Society Reviews
https://www.readbyqxmd.com/read/28515944/identifying-baseline-immune-related-biomarkers-to-predict-clinical-outcome-of-immunotherapy
#6
REVIEW
Sacha Gnjatic, Vincenzo Bronte, Laura Rosa Brunet, Marcus O Butler, Mary L Disis, Jérôme Galon, Leif G Hakansson, Brent A Hanks, Vaios Karanikas, Samir N Khleif, John M Kirkwood, Lance D Miller, Dolores J Schendel, Isabelle Tanneau, Jon M Wigginton, Lisa H Butterfield
As cancer strikes, individuals vary not only in terms of factors that contribute to its occurrence and development, but as importantly, in their capacity to respond to treatment. While exciting new therapeutic options that mobilize the immune system against cancer have led to breakthroughs for a variety of malignancies, success is limited to a subset of patients. Pre-existing immunological features of both the host and the tumor may contribute to how patients will eventually fare with immunotherapy. A broad understanding of baseline immunity, both in the periphery and in the tumor microenvironment, is needed in order to fully realize the potential of cancer immunotherapy...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28515317/characterization-of-a-secretory-hydrolase-from-mycobacterium-tuberculosis-sheds-critical-insight-into-host-lipid-utilization-by-m-tuberculosis
#7
Khundrakpam Herojit Singh, Bhavya Jha, Abhisek Dwivedy, Eira Choudhary, Arpitha G N, Anam Ashraf, Nisheeth Agarwal, Bichitra Kumar Biswal
Mycobacterium tuberculosis causes tuberculosis in humans and predominantly infects alveolar macrophages. To survive inside host lesions and to evade immune surveillance, this pathogen has developed many strategies. For example, M. tuberculosis uses host-derived lipids/fatty acids as nutrients for prolonged persistence within hypoxic host microenvironments. M. tuberculosis imports these metabolites through its respective transporters, and in the case of host fatty acids, a pertinent question arises: does M. tuberculosis have the enzyme(s) for cleavage of fatty acids from host lipids? We show herein that a previously uncharacterized membrane-associated M...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28514770/mm-bmscs-induce-na%C3%A3-ve-cd4-t-lymphocytes-dysfunction-through-fibroblast-activation-protein-%C3%AE
#8
Xiaofei Wu, Yadan Wang, Jian Xu, Ting Luo, Jun Deng, Yu Hu
BACKGROUND: The tumor microenvironment plays a major role in multiple myelomas (MM). MM-BMSCs (bone marrow mesenchymal stromal cells) can support tumor growth and immune surveillance escape. On the other hand, fibroblast activation protein α, expressed by cancer stroma cells including BMSCs, has been shown to potentiate epithelial cancers growth and immune suppression. RESULTS: MM-BMSC inhibited proliferation of T cells (P = 0.0138), promoted senescence of T cells (P < 0...
April 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28514674/mentoring-immunity-mtor-signaling-in-the-development-and-function-of-tissue-resident-immune-cells
#9
REVIEW
Russell G Jones, Edward J Pearce
Tissue-resident immune cells must balance survival in peripheral tissues with the capacity to respond rapidly upon infection or tissue damage, and in turn couple these responses with intrinsic metabolic control and conditions in the tissue microenvironment. The serine/threonine kinase mammalian/mechanistic target of rapamycin (mTOR) is a central integrator of extracellular and intracellular growth signals and cellular metabolism and plays important roles in both innate and adaptive immune responses. This review discusses the function of mTOR signaling in the differentiation and function of tissue-resident immune cells, with focus on the role of mTOR as a metabolic sensor and its impact on metabolic regulation in innate and adaptive immune cells...
May 16, 2017: Immunity
https://www.readbyqxmd.com/read/28513269/immune-surveillance-in-melanoma-from-immune-attack-to-melanoma-escape-and-even-counterattack
#10
Fade Mahmoud, Bradley Shields, Issam Makhoul, Nathan Avaritt, Henry K Wong, Laura F Hutchins, Sara Shalin, Alan J Tackett
Pharmacologic inhibition of the cytotoxic T lymphocyte antigen 4 (CTLA4) and the programmed death receptor-1 (PD1) has resulted in unprecedented durable responses in metastatic melanoma. However, resistance to immunotherapy remains a major challenge. Effective immune surveillance against melanoma requires four essential steps: activation of the T lymphocytes, homing of the activated T lymphocytes to the melanoma microenvironment, identification and attack of melanoma cells by activated T lymphocytes, and the sensitivity of melanoma cells to apoptosis...
May 17, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28512922/effect-of-chemical-immobilization-of-sdf-1%C3%AE-into-muscle-derived-scaffolds-on-angiogenesis-and-muscle-progenitor-recruitment
#11
Sareh Rajabi-Zeleti, Sasan Jalili-Firoozinezhad, Mohammad Kazemi Ashtiani, Gilles Le Carrou, Shahragim Tajbakhsh, Hossein Baharvand
The availability of three-dimensional bioactive scaffolds with enhanced angiogenic capacity that have the capability to recruit tissue specific resident progenitors is of great importance for the regeneration of impaired skeletal muscle. Here we have investigated whether introduction of chemoattractant factors to tissue specific extracellular matrix (ECM) promotes cellular behavior in vitro as well as muscle progenitor recruitment and vascularization in vivo. We developed an interconnective macroporous sponge from decellularized skeletal muscle with maintained biochemical traits of the intact muscle...
May 16, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28512172/in-vivo-hemin-conditioning-targets-the-vascular-and-immunological-compartments-and-restrains-prostate-tumor-development
#12
Felipe M Jaworski, Lucas Gentilini, Geraldine Gueron, Roberto P Meiss, Emiliano G Ortiz, Paula M Berguer, Asif Ahmed, Nora M Navone, Gabriel A Rabinovich, Daniel Compagno, Diego J Laderach, Elba S Vazquez
Purpose: Conditioning strategies constitute a relatively unexplored and exciting opportunity to shape tumor fate by targeting the tumor microenvironment. In this study we assessed how hemin, a pharmacological inducer of Heme Oxygenase-1 (HO-1), impacts upon prostate cancer (PCa) development in an in vivo conditioning model. <p>Experimental Design: The stroma of C57BL/6 mice was conditioned by subcutaneous administration of hemin prior to TRAMP-C1 tumor challenge. Complementary in vitro and in vivo assays were performed to evaluate hemin effect on both angiogenesis and the immune response...
May 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28511092/epigenetics-and-immunotherapy-the-current-state-of-play
#13
REVIEW
Jennifer Dunn, Sudha Rao
Cancer cells employ a number of mechanisms to escape immunosurveillance and facilitate tumour progression. The recent explosion of interest in immunotherapy, especially immune checkpoint blockade, is a result of discoveries about the fundamental ligand-receptor interactions that occur between immune and cancer cells within the tumour microenvironment. Distinct ligands expressed by cancer cells engage with cell surface receptors on immune cells, triggering inhibitory pathways (such as PD-1/PD-L1) that render immune cells immunologically tolerant...
May 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28511073/preparation-and-evaluation-of-l-and-d-5-18-f-fluorotryptophan-as-pet-imaging-probes-for-indoleamine-and-tryptophan-2-3-dioxygenases
#14
Tang Tang, Herman S Gill, Annie Ogasawara, Jeff N Tinianow, Alexander N Vanderbilt, Simon-Peter Williams, Georgia Hatzivassiliou, Sharla White, Wendy Sandoval, Kevin DeMent, Mengling Wong, Jan Marik
Indoleamine and tryptophan 2,3-dioxygenases (IDO1 and TDO2) are pyrrolases catalyzing the oxidative cleavage of the 2,3-double bond of L-tryptophan in kynurenine pathway. In the tumor microenvironment, their increased activity prevents normal immune function, i.e. tumor cell recognition and elimination by cytotoxic T-cells. Consequently, inhibition of the kynurenine pathway may enhance the activity of cancer immunotherapeutics by reversing immune dysfunction. We sought to investigate the properties of radiolabeled 5-[(18)F]fluorotryptophan with respect to its ability for measuring IDO1 and TDO2 activity by positron emission tomography (PET)...
May 5, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28509673/immune-responses-to-invasive-aspergillosis-new-understanding-and-therapeutic-opportunities
#15
Tobias M Hohl
PURPOSE OF REVIEW: Invasive aspergillosis is a worldwide disease that primarily affects immune-compromised patients, agricultural workers with corneal abrasions, individuals with structural lung disease, and patients with primary immune deficiency. The critical function of the immune system is to prevent the germination of airborne conidia into tissue-invasive hyphae. This review covers recent advances that shape our understanding of anti-Aspergillus immunity at the molecular and cellular level...
May 13, 2017: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/28508352/pediatric-precursor-b-acute-lymphoblastic-leukemia-are-t-helper-cells-the-missing-link-in-the-infectious-etiology-theory
#16
REVIEW
Simone Bürgler, David Nadal
Precursor B acute lymphoblastic leukemia (BCP-ALL), the most common childhood malignancy, arises from an expansion of malignant B cell precursors in the bone marrow. Epidemiological studies suggest that infections or immune responses to infections may promote such an expansion and thus BCP-ALL development. Nevertheless, a specific pathogen responsible for this process has not been identified. BCP-ALL cells critically depend on interactions with the bone marrow microenvironment. The bone marrow is also home to memory T helper (Th) cells that have previously expanded during an immune response in the periphery...
December 2017: Molecular and Cellular Pediatrics
https://www.readbyqxmd.com/read/28508153/cellular-and-molecular-perspectives-in-rheumatoid-arthritis
#17
REVIEW
Douglas J Veale, Carl Orr, Ursula Fearon
Synovial immunopathology in rheumatoid arthritis is complex involving both resident and infiltrating cells. The synovial tissue undergoes significant neovascularization, facilitating an influx of lymphocytes and monocytes that transform a typically acellular loose areolar membrane into an invasive tumour-like pannus. The microvasculature proliferates to form straight regularly-branching vessels; however, they are highly dysfunctional resulting in reduced oxygen supply and a hypoxic microenvironment. Autoantibodies such as rheumatoid factor and anti-citrullinated protein antibodies are found at an early stage, often before arthritis has developed, and they have been implicated in the pathogenesis of RA...
May 15, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/28507803/pd-l1-expression-on-malignant-cells-is-no-prerequisite-for-checkpoint-therapy
#18
Jan Willem Kleinovink, Koen A Marijt, Mark J A Schoonderwoerd, Thorbald van Hall, Ferry Ossendorp, Marieke F Fransen
Immunotherapy with PD-1/PD-L1-blocking antibodies is clinically effective for several tumor types, but the mechanism is not fully understood. PD-L1 expression on tumor biopsies is generally regarded as an inclusion criterion for this cancer therapy. Here, we describe the PD-L1-blocking therapeutic responses of preclinical tumors in which PD-L1 expression was removed from cancer cells, but not from immune infiltrate. Lack of PD-L1 expression on malignant cells delayed tumor outgrowth in a CD8(+) T cell-mediated fashion, showing the importance of this molecule in immune suppression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507802/b-cells-and-the-humoral-response-in-melanoma-the-overlooked-players-of-the-tumor-microenvironment
#19
REVIEW
Giulia Chiaruttini, Silvia Mele, James Opzoomer, Silvia Crescioli, Kristina M Ilieva, Katie E Lacy, Sophia N Karagiannis
Evidence of tumor-resident mature B cell and antibody compartments and reports of associations with favorable prognosis in malignant melanoma suggest that humoral immunity could participate in antitumor defense. Likely striving to confer immunological protection while being subjected to tumor-promoting immune tolerance, B cells may engender multiple functions, including antigen processing and presentation, cytokine-mediated signaling, antibody class switching, expression and secretion. We review key evidence in support of multifaceted immunological mechanisms by which B cells may counter or contribute to malignant melanoma, and we discuss their potential translational implications...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507795/digital-analysis-and-epigenetic-regulation-of-the-signature-of-rejection-in-colorectal-cancer
#20
Viktor H Koelzer, Lena Sokol, Stefan Zahnd, Lucine Christe, Heather Dawson, Martin D Berger, Daniel Inderbitzin, Inti Zlobec, Alessandro Lugli
The immune system plays a pivotal role in the development and progression of colorectal cancer (CRC). Tumor immune rejection has been previously linked to the activation of the interferon-stimulated genes (ISG) STAT1, IRF-5 and IRF-1. Specific immunoregulatory microRNAs (miRNAs) may impact the expression of these ISG in the tumor microenvironment. In this translational study, we develop a digital image analysis protocol to identify the ISG-gene expression signature and investigate miRNA expression in the immediate environment of invading cancer cells...
2017: Oncoimmunology
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