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https://www.readbyqxmd.com/read/29668066/mait-cell-mediated-cytotoxicity-roles-in-host-defense-and-therapeutic-potentials-in-infectious-diseases-and-cancer
#1
REVIEW
Patrick T Rudak, Joshua Choi, S M Mansour Haeryfar
Mucosa-associated invariant T (MAIT) cells are unconventional, innate-like T lymphocytes that sense the presence of MHC-related protein 1 (MR1)-restricted ligands and select inflammatory cues. Consequently, they release potent immunomodulatory mediators, including IFN-γ, TNF-α, and/or IL-17. MAIT cells can also be viewed as killer cells. They display several NK cell-associated receptors, carry granules containing cytotoxic effector molecules, and swiftly upregulate perforin and granzymes upon activation. Accordingly, MAIT cells are capable of lysing MR1-expressing cells infected with a variety of pathogenic bacteria in in vitro settings and may also mount cytotoxic responses during microbial infections in vivo...
April 18, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29667847/cd47-is-a-novel-potent-immunotherapy-target-in-human-malignancies-current-studies-and-future-promises
#2
Bing Tong, Mengzhao Wang
Recently, many immunosuppressive checkpoints such as PD-L1, CTLA-4 and CD47, were identified in succession and serve as potential immunotherapy targets in human cancers. Among them, CD47, a 'marker-of-self' protein that is overexpressed broadly across tumor types, is emerging as a novel potent macrophage immune checkpoint for cancer immunotherapy. In this review, we highlight the prominent role of CD47 as a 'don't-eat-me' signal that inhibits macrophage phagocytosis for immune evasion of a tumor and presents the opportunities and challenges for CD47 inhibitors both as monotherapy and in combination treatments for hematological cancers and solid tumors; some of these agents are currently in clinical trials...
April 18, 2018: Future Oncology
https://www.readbyqxmd.com/read/29667553/car-t-cell-therapy-a-new-era-in-cancer-immunotherapy
#3
Miliotou N Androulla, Papadopoulou C Lefkothea
BACKGROUND: Cancer is one of the leading causes of death worldwide. Over the years, a number of conventional cytotoxic approaches for neoplastic diseases has been developed. However, due to their limited effectiveness in accordance with the heterogeneity of cancer cells, there is a constant search for therapeutic approaches with improved outcome, such as immunotherapy that utilizes and enhances the normal capacity of the patient's immune system. METHODS: Chimeric Antigen Receptor (CAR) T-cell therapy involves genetic modification of patient's autologous T-cells to express a CAR specific for a tumor antigen, following by ex vivo cell expansion and re-infusion back to the patient...
April 17, 2018: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/29667346/in-situ-vaccination-harvesting-low-hanging-fruit-on-the-cancer-immunotherapy-tree
#4
REVIEW
Mee Rie Sheen, Steven Fiering
After 100 years of debate, it is clear that cancer is recognized by the immune system and this has generated immense interest in cancer immunotherapy. The systemic nature of the immune system gives immunotherapy the ability to treat metastatic disease, which currently requires chemotherapy that frequently fails. Like chemotherapy, most immunotherapy is systemically applied in an effort to generate systemic antitumor immune response. However, local administration of immunostimulatory reagents into a recognized tumor by in situ vaccination (ISV) can also generate systemic antitumor immunity to fight metastatic disease...
April 18, 2018: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
https://www.readbyqxmd.com/read/29667271/syndrome-and-outcome-of-antibody-negative-limbic-encephalitis
#5
Francesc Graus, Domingo Escudero, Laura Oleaga, Jordi Bruna, Alberto Villarejo-Galende, Jordi Ballabriga, María Inés Barceló, Francisco Gilo, Stoyan Popkirov, Pavel Stourac, Josep Dalmau
OBJECTIVE: To report the clinical characteristics of 12 patients with limbic encephalitis (LE) who were antibody-negative after a comprehensive immunological study. METHODS: Review of clinical records of 163 patients with LE. Immunohistochemistry on rat brain, cultured neurons, and cell-based assays were used to identify neuronal autoantibodies. Patients were included if 1) there was adequate clinical, CSF, and MRI information to classify the syndrome as LE, 2) MRI images were accesible for central review, and 3) serum and CSF were available and confirmed negative for neuronal antibodies...
April 18, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/29667169/expression-of-scavenger-receptor-marco-defines-a-targetable-tumor-associated-macrophage-subset-in-non-small-cell-lung-cancer
#6
Linnéa La Fleur, Vanessa F Boura, Andrey Alexeyenko, Anders Berglund, Victor Pontén, Johanna Sm Mattsson, Dijana Djureinovic, Johan Persson, Hans Brunnström, Johan Isaksson, Eva Brandén, Hirsh Koyi, Patrick Micke, Mikael Ci Karlsson, Johan Botling
Tumor-associated macrophages (TAMs) are attractive targets for immunotherapy. Recently, studies in animal models showed that treatment with an anti-TAM antibody directed against the scavenger receptor MARCO resulted in suppression of tumor growth and metastatic dissemination. Here we investigated the expression of MARCO in relation to other macrophage markers and immune pathways in a non-small cell lung cancer (NSCLC) cohort (n=352). MARCO, CD68, CD163, MSR1 and programmed death ligand-1 (PD-L1) were analyzed by immunohistochemistry and immunofluorescence, and associations to other immune cells and regulatory pathways were studied in a subset of cases (n=199) with available RNA-seq data...
April 18, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29666625/dying-to-be-noticed-epigenetic-regulation-of-immunogenic-cell-death-for-cancer-immunotherapy
#7
REVIEW
Brianne Cruickshank, Michael Giacomantonio, Paola Marcato, Sherri McFarland, Jonathan Pol, Shashi Gujar
Immunogenic cell death (ICD) activates both innate and adaptive arms of the immune system during apoptotic cancer cell death. With respect to cancer immunotherapy, the process of ICD elicits enhanced adjuvanticity and antigenicity from dying cancer cells and consequently, promotes the development of clinically desired antitumor immunity. Cancer ICD requires the presentation of various "hallmarks" of immunomodulation, which include the cell-surface translocation of calreticulin, production of type I interferons, and release of high-mobility group box-1 and ATP, which through their compatible actions induce an immune response against cancer cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29666300/a-pan-cancer-landscape-of-interactions-between-solid-tumors-and-infiltrating-immune-cell-populations
#8
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/29665944/-current-status-and-challenges-of-car-t-immunotherapy-in-hematologic-malignancies-review
#9
Xin Cheng, Ya-Jie Wang, Shuai Feng, Ya-Yun Wu, Tong-Hua Yang, Xun Lai
The chimeric antigen receptor (CAR) T cell therapy has gradually became a new trend in the treatment of refractory and relapsed hematologic malignancies by developing for 30 years. With the exciting development of genetic engineering, CAR-T technology has subjected to 4 generations of innovation. Structure of CAR-T started from a single signal molecule to 2 or more than 2 co-stimulatory molecules, and then coding the CAR gene or promoter. CAR-T can specifically recognize tumor antigens, and does not be restricted by major histocompatibility complex (MHC), thus making a breakthrough in clinical treatment...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29665853/microsatellite-instability-in-prostate-cancer-by-pcr-or-next-generation-sequencing
#10
Jennifer A Hempelmann, Christina M Lockwood, Eric Q Konnick, Michael T Schweizer, Emmanuel S Antonarakis, Tamara L Lotan, Bruce Montgomery, Peter S Nelson, Nola Klemfuss, Stephen J Salipante, Colin C Pritchard
BACKGROUND: Microsatellite instability (MSI) is now being used as a sole biomarker to guide immunotherapy treatment for men with advanced prostate cancer. Yet current molecular diagnostic tests for MSI have not been evaluated for use in prostate cancer. METHODS: We evaluated two next-generation sequencing (NGS) MSI-detection methods, MSIplus (18 markers) and MSI by Large Panel NGS (> 60 markers), and compared the performance of each NGS method to the most widely used 5-marker MSI-PCR detection system...
April 17, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29665677/a-nanoscale-metal-organic-framework-overcomes-hypoxia-for-photodynamic-therapy-primed-cancer-immunotherapy
#11
Guangxu Lan, Kaiyuan Ni, Ziwan Xu, Samuel S Veroneau, Yang Song, Wenbin Lin
Immunotherapy has become a promising cancer therapy, but only works for a subset of cancer patients. Immunogenic photodynamic therapy (PDT) can prime cancer immunotherapy to increase the response rates, but its efficacy is severely limited by tumor hypoxia. Here we report a nanoscale metal-organic framework, Fe-TBP, as a novel nanophotosensitizer to overcome tumor hypoxia and sensitize effective PDT, priming non-inflamed tumors for cancer immunotherapy. Fe-TBP was built from iron clusters and porphyrin ligands and sensitized PDT under both normoxic and hypoxic conditions...
April 18, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29665588/current-technique-and-application-of-percutaneous-cryotherapy
#12
Andreas H Mahnken, Alexander Marc König, Jens Holger Figiel
PURPOSE:  Local ablative therapies have become an established treatment option in interventional oncology. Radiofrequency ablation (RFA) and microwave ablation (MWA) are a standard of care in the treatment of hepatocellular carcinoma (HCC). Currently, there is an increasing interest in cryotherapy, one of the oldest ablation techniques. It has some unique characteristics with regard to technology and mechanism of action. MATERIALS AND METHODS:  A systematic literature search using the terms cryotherapy, cryosurgery and cryoablation was performed...
April 17, 2018: RöFo: Fortschritte Auf Dem Gebiete der Röntgenstrahlen und der Nuklearmedizin
https://www.readbyqxmd.com/read/29664561/the-function-and-dysfunction-of-memory-cd8-t-cells-in-tumor-immunity
#13
REVIEW
James L Reading, Felipe Gálvez-Cancino, Charles Swanton, Alvaro Lladser, Karl S Peggs, Sergio A Quezada
The generation and maintenance of CD8+ T cell memory is crucial to long-term host survival, yet the basic tenets of CD8+ T cell immunity are still being established. Recent work has led to the discovery of tissue-resident memory cells and refined our understanding of the transcriptional and epigenetic basis of CD8+ T cell differentiation and dysregulation. In parallel, the unprecedented clinical success of immunotherapy has galvanized an intense, global research effort to decipher and de-repress the anti-tumor response...
May 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29664013/%C3%AE-catenin-mediated-immune-evasion-pathway-frequently-operates-in-primary-cutaneous-melanomas
#14
Jérémie Nsengimana, Jon Laye, Anastasia Filia, Sally O'Shea, Sathya Muralidhar, Joanna Poźniak, Alastair Droop, May Chan, Christy Walker, Louise Parkinson, Joanne Gascoyne, Tracey Mell, Minttu Polso, Rosalyn Jewell, Juliette Randerson-Moor, Graham P Cook, D Timothy Bishop, Julia Newton-Bishop
Immunotherapy prolongs survival in only a subset of melanoma patients, highlighting the need to better understand the driver tumor microenvironment. We conducted bioinformatic analyses of 703 transcriptomes to probe the immune landscape of primary cutaneous melanomas in a population-ascertained cohort. We identified and validated 6 immunologically distinct subgroups, with the largest having the lowest immune scores and the poorest survival. This poor-prognosis subgroup exhibited expression profiles consistent with β-catenin-mediated failure to recruit CD141+ DCs...
April 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29663929/generation-of-a-graft-versus-anticancer-immune-response-through-skin-allograft-with-tumor
#15
Yuan Fang, Sufang Zhou, Baoshi Zheng, Wenlin Gong, Yong Huang, Zhenghua Zhang, Chaofan Zhou, Huiling Wang, Zhimei Huang, Liping Zhong, Yongxiang Zhao
Effector memory T cells (TEM) are a subset of memory T cells which play an important role in stimulation of adaptive immunity. Although they are associated with multiple immune responses, the antitumor effect of TEM is not clearly understood. In this research, generation of anti-tumor TEM was induced through skin allografts in C57BL/6 mice with B16 melanoma. We observed that the growth of tumor tissues in C57BL/6 mice treated with allografts was interrupted. Furthermore, the survival time for the treated mice was prolonged along with increased serum levels for CXCL9, CXCL10 and INF-γ...
March 1, 2018: Journal of Biomedical Nanotechnology
https://www.readbyqxmd.com/read/29663340/molecular-signatures-in-hepatocellular-carcinoma-a-step-toward-rationally-designed-cancer-therapy
#16
REVIEW
Derek J Erstad, Bryan C Fuchs, Kenneth K Tanabe
Molecular characterization of hepatocellular carcinoma (HCC) has greatly improved our understanding of disease pathogenesis. Mutational analysis, RNA and microRNA expression profiling, and epigenetic characterization have revealed common aberrations in oncogenes and tumor suppressors that correlate with disease biology and serve as a guide for the rational design of targeted therapies. These approaches have also led to the discovery of novel targets, including mutations in isocitrate dehydrogenase and chromatin remodeling enzymes...
April 17, 2018: Cancer
https://www.readbyqxmd.com/read/29662667/genetically-enhanced-t-lymphocytes-and-the-intensive-care-unit
#17
REVIEW
Tiberiu Tat, Huming Li, Catalin-Sorin Constantinescu, Anca Onaciu, Sergiu Chira, Ciprian Osan, Sergiu Pasca, Bobe Petrushev, Vlad Moisoiu, Wilhelm-Thomas Micu, Cristian Berce, Sebastian Tranca, Delia Dima, Ioana Berindan-Neagoe, Jianliang Shen, Ciprian Tomuleasa, Liren Qian
Chimeric antigen receptor-modified T cells (CAR-T cells) and donor lymphocyte infusion (DLI) are important protocols in lymphocyte engineering. CAR-T cells have emerged as a new modality for cancer immunotherapy due to their potential efficacy against hematological malignancies. These genetically modified receptors contain an antigen-binding moiety, a hinge region, a transmembrane domain, and an intracellular costimulatory domain resulting in lymphocyte T cell activation subsequent to antigen binding. In present-day medicine, four generations of CAR-T cells are described depending on the intracellular signaling domain number of T cell receptors...
March 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29662615/transcriptome-and-proteome-profiling-reveals-stress-induced-expression-signatures-of-imiquimod-treated-tasmanian-devil-facial-tumor-disease-dftd-cells
#18
Amanda L Patchett, Richard Wilson, Jac C Charlesworth, Lynn M Corcoran, Anthony T Papenfuss, Bruce A Lyons, Gregory M Woods, Cesar Tovar
As a topical cancer immunotherapy, the toll-like receptor 7 ligand imiquimod activates tumor regression via stimulation of immune cell infiltration and cytotoxic responses. Imiquimod also exerts direct pro-apoptotic effects on tumor cells in vitro , but a role for these effects in imiquimod-induced tumor regression remains undefined. We previously demonstrated that cell lines derived from devil facial tumor disease (DFTD), a transmissible cancer threatening the survival of the Tasmanian devil ( Sarcophilus harrisii ), are sensitive to imiquimod-induced apoptosis...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29662547/pd-l1-expression-testing-in-non-small-cell-lung-cancer
#19
REVIEW
Cristina Teixidó, Noelia Vilariño, Roxana Reyes, Noemí Reguart
In recent years, immunotherapy has revolutionized and changed the standard of care in patients with advanced non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors, fundamentally those that act by blocking the programmed cell death receptor-1 (PD-1) and its ligand the programmed cell death ligand-1 (PD-L1) have emerged as novel treatment strategies in NSCLC, demonstrating undoubted superiority over chemotherapy in terms of efficacy. Several of these immune checkpoint modulators have recently gained regulatory approval for the treatment of advanced NSCLC, such as nivolumab, atezolizumab and pembrolizumab in first-line (only the latter) and second-line settings, and more recently, durvalumab as maintenance after chemoradiotherapy in locally advanced disease...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29662546/combination-of-immunotherapy-with-chemotherapy-and-radiotherapy-in-lung-cancer-is-this-the-beginning-of-the-end-for-cancer
#20
REVIEW
Chiara Lazzari, Niki Karachaliou, Alessandra Bulotta, Mariagrazia Viganó, Aurora Mirabile, Elena Brioschi, Mariacarmela Santarpia, Luca Gianni, Rafael Rosell, Vanesa Gregorc
Immune checkpoint inhibitors have significantly improved overall survival with an acceptable safety profile in a substantial proportion of non-small cell lung cancer (NSCLC) patients. However, not all patients are sensitive to immune checkpoint blockade and, in some cases, programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors accelerate tumor progression. Several combination strategies are under evaluation, including the concomitant or sequential evaluation of chemotherapy or radiotherapy with immunotherapy...
2018: Therapeutic Advances in Medical Oncology
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