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Immune checkpoint therapy

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https://www.readbyqxmd.com/read/28099367/antiphospholipid-syndrome-associated-with-combined-immune-checkpoint-inhibitor-therapy
#1
Arjun Gupta, Udayan Shah, Htet Khine, Travis Vandergriff, Thomas Froehlich
No abstract text is available yet for this article.
January 17, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28096506/targeting-tnfr2-an-immune-checkpoint-stimulator-and-oncoprotein-is-a-promising-treatment-for-cancer
#2
REVIEW
Xin Chen, Joost J Oppenheim
Tumor necrosis factor receptor 2 (TNFR2) is expressed both by some cancer cells and by tumor-infiltrating immunosuppressive CD4(+)FoxP3(+) regulatory T cells (Tregs). TNFR2 stimulates the activation and proliferation of Tregs, a major checkpoint of antitumor immune responses, and promotes cancer cell survival and tumor growth. In this issue of Science Signaling, Torrey et al found that dominant antagonistic antibodies against human TNFR2 may be a potential therapy for ovarian cancer patients by simultaneously suppressing Treg activity and inducing the death of the cancer cells...
January 17, 2017: Science Signaling
https://www.readbyqxmd.com/read/28094262/radiotherapy-and-immunotherapy-a-beneficial-liaison
#3
REVIEW
Ralph R Weichselbaum, Hua Liang, Liufu Deng, Yang-Xin Fu
Investigations into the interaction between radiotherapy and the host immune system have uncovered new mechanisms that can potentially be exploited to improve the efficacy of radiotherapy. Radiation promotes the release of danger signals and chemokines that recruit inflammatory cells into the tumour microenvironment, including antigen-presenting cells that activate cytotoxic T-cell function. By contrast, radiation can attract immunosuppressive cells into the tumour microenvironment. In rare circumstances, the antitumour effect of radiotherapy has been observed outside of the radiation field, known as the abscopal effect...
January 17, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28090751/a-safety-checkpoint-to-eliminate-cancer-risk-of-the-immune-evasive-cells-derived-from-human-embryonic-stem-cells
#4
Jingjin He, Zhili Rong, Xuemei Fu, Yang Xu
Human embryonic stem cells (hESCs) hold great promise in the regenerative therapy of many currently untreatable human diseases. One of the key bottlenecks is the immune rejection of hESC-derived allografts by the recipient. To overcome this challenge, we have established new approaches to induce immune protection of hESC-derived allografts through the co-expression of immune suppressive molecules CTLA4-Ig and PD-L1. However, this in turn raises a safety concern of cancer risk because these hESC-derived cells can evade immune surveillance...
January 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28088061/galectins-emerging-regulatory-checkpoints-linking-tumor-immunity-and-angiogenesis
#5
REVIEW
Santiago P Méndez-Huergo, Ada G Blidner, Gabriel A Rabinovich
Immune checkpoints, a plethora of inhibitory pathways aimed at maintaining immune cell homeostasis, may be co-opted by cancer cells to evade immune destruction. Therapies targeting immune checkpoints have reached a momentum yielding significant clinical benefits in patients with various malignancies by unleashing anti-tumor immunity. Galectins, a family of glycan-binding proteins, have emerged as novel regulatory checkpoints that promote immune evasive programs by inducing T-cell exhaustion, limiting T-cell survival, favoring expansion of regulatory T cells, de-activating natural killer cells and polarizing myeloid cells toward an immunosuppressive phenotype...
January 11, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28076863/adverse-renal-effects-of-immune-checkpoint-inhibitors-a-narrative-review
#6
Rimda Wanchoo, Sabine Karam, Nupur N Uppal, Valerie S Barta, Gilbert Deray, Craig Devoe, Vincent Launay-Vacher, Kenar D Jhaveri
BACKGROUND: Cancer immunotherapy, such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death 1 (PD-1), has revolutionized the treatment of malignancies by engaging the patient's own immune system against the tumor rather than targeting the cancer directly. These therapies have demonstrated a significant benefit in the treatment of melanomas and other cancers. SUMMARY: In order to provide an extensive overview of the renal toxicities induced by these agents, a Medline search was conducted of published literature related to ipilimumab-, pembrolizumab-, and nivolumab-induced kidney toxicity...
January 12, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/28073132/hypothyroidism-in-cancer-patients-on-immune-checkpoint-inhibitors-with-anti-pd1-agents-insights-on-underlying-mechanisms
#7
M Alhusseini, J Samantray
Background: Immune therapy using monoclonal antibodies against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death 1 receptor (PD-1) for various cancers have been reported to cause thyroid dysfunction. Little is known, however, about the underlying pathogenic mechanisms and the course of hypothyroidism that subsequently develops. In this report, we use the change in thyroglobulin and thyroid antibody levels in patients on immune therapy who develop hypothyroidism to better understand its pathogenesis as well as examine the status of hypothyroidism in the long term...
January 10, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28064556/pd-1-checkpoint-blockade-alone-or-combined-pd-1-and-ctla-4-blockade-as-immunotherapy-for-lung-cancer
#8
Tawee Tanvetyanon, Jhanelle E Gray, Scott J Antonia
Signaling through T-cell surface, an immune checkpoint protein such as PD-1 or CTLA-4 helps dampen or terminate unwanted immune responses. Blocking a single immune checkpoint or multiple checkpoints simultaneously can generate anti-tumor activity against a variety of cancers including lung cancer. Area covered: This review highlights the results of recent clinical studies of single or combination checkpoint inhibitor immunotherapy in non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC). The authors discuss pembrolizumab and pembrolizumab plus ipilimumab, durvalumab and durvalumab plus tremelimumab, nivolumab and nivolumab plus ipilimumab for NSCLC as well as nivolumab and nivolumab plus ipilimumab for SCLC...
January 18, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28063623/immune-checkpoint-inhibitors-in-lung-cancer-an-unheralded-opportunity
#9
R Marshall, A Popple, T Kordbacheh, J Honeychurch, C Faivre-Finn, T Illidge
Lung cancer remains the leading cause of cancer-related death worldwide, with non-small cell lung cancer accounting for 85% of the disease. Over 70% of patients present with locally advanced, non-resectable or metastatic disease and despite improvements in chemoradiotherapy regimens and the development of molecularly targeted agents, 5 year survival rates remain poor, with acquired resistance to novel targeted therapies becoming a growing concern. Currently there remains an unmet need in effectively treating and inducing durable responses in advanced disease...
January 4, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28062906/programmed-cell-death-1-pathway-inhibition-in-myeloid-malignancies-implications-for-myeloproliferative-neoplasms
#10
REVIEW
D C Choi, D Tremblay, C Iancu-Rubin, J Mascarenhas
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic diseases that belong to the spectrum of myeloid malignancies (MyMs), which also include myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelogenous leukemia (CML). While hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic approach to many MyMs, the associated morbidity and mortality have necessitated the development of non-HSCT therapeutics for symptom management and disease course modification...
January 6, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28061473/immunotherapy-incorporation-in-the-evolving-paradigm-of-renal-cancer-management-and-future-prospects
#11
Kenneth G Liu, Sorab Gupta, Sanjay Goel
Significant progress has been made in the management of renal cell carcinoma (RCC) during the last few decades. In early stage, localized disease, surgical resection remains the modality of choice, with no therapeutic interventions as options for post-operative therapy other than simple observation and clinical surveillance. However, treatment options in the advanced or metastatic setting are increasing at a dizzying pace, initially with cytokine therapy, then with the increased availability of targeted therapy including novel small-molecule inhibitors of receptor tyrosine kinases and monoclonal antibodies targeting novel proteins, establishing them as the current standard of care...
December 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/28061465/sirp%C3%AE-antibody-fusion-proteins-stimulate-phagocytosis-and-promote-elimination-of-acute-myeloid-leukemia-cells
#12
Laia Pascual Ponce, Nadja C Fenn, Nadine Moritz, Christina Krupka, Jan-Hendrik Kozik, Kirsten Lauber, Marion Subklewe, Karl-Peter Hopfner
CD47, expressed on a variety of tumor cells, confers immune resistance by delivering an inhibitory "don't eat me" signal to phagocytic cells via its myeloid-specific receptor SIRPα. Recent studies have shown that blocking the CD47-SIRPα axis with CD47-directed antibodies or antibody-derivatives enhances phagocytosis and increases antitumor immune effects. However, CD47 expression on healthy cells creates an antigen sink and potential sites of toxicity, limiting the efficacy of CD47-directed therapies. In this study, we first characterized CD47 expression in Acute Myeloid Leukemia (AML) patients (n = 213) and found that CD47 is highly expressed on both AML bulk and stem cells irrespective of the disease state...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28059852/immune-checkpoint-inhibitors-in-first-line-therapy-of-advanced-non-small-cell-lung-cancer
#13
Jordi Remon, Benjamin Besse
PURPOSE OF REVIEW: Evading immune destruction is a hallmark of cancer. The first therapeutic wave in immunotherapies comprised a series of monoclonal antibodies directed against the immune checkpoint molecules cytotoxic T-lymphocyte-associated protein 4, programmed death 1 (PD-1), and programmed death ligand-1 (PD-L1) revolutionizing the therapeutic landscape of advanced non-small cell lung cancer. They were validated initially as second-line treatment, becoming the new standard of care...
January 3, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28057932/dynamic-versus-static-biomarkers-in-cancer-immune-checkpoint-blockade-unravelling-complexity
#14
W Joost Lesterhuis, Anthony Bosco, Michael J Millward, Michael Small, Anna K Nowak, Richard A Lake
Recently, there has been a coordinated effort from academic institutions and the pharmaceutical industry to identify biomarkers that can predict responses to immune checkpoint blockade in cancer. Several biomarkers have been identified; however, none has reliably predicted response in a sufficiently rigorous manner for routine use. Here, we argue that the therapeutic response to immune checkpoint blockade is a critical state transition of a complex system. Such systems are highly sensitive to initial conditions, and critical transitions are notoriously difficult to predict far in advance...
January 6, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28057176/immunoth%C3%A3-rapie-et-m%C3%A3-lanome-l%C3%A2-exemple-des-anticorps-immunomodulateurs
#15
Cécile Pagès, Barouyr Baroudjian, Celeste Lebbé
Recently, metastatic melanoma has known real therapeutic improvement. Since 2011, 8 drugs have been approved for advanced melanoma such as immunotherapy checkpoint inhibitors. Chemotherapy is no longer used in the first setting of metastatic melanoma treatment. In 2010, the advent of ipilimumab, an anti CTLA 4 inhibitor, changed the scenario and in the following years, many studies confirmed the efficacy of nivolumab and pembrolizumab, two anti PD 1 inhibitors, as a first line treatment. Furthermore, the combination of first-line nivolumab plus ipilimumab might lead to improved outcomes compared with first-line ipilimumab alone in patients with advanced melanoma...
November 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/28055269/targeting-pd-1-pathway-a-new-hope-for-gastrointestinal-cancers
#16
Burak Bilgin, Mehmet An Sendur, Muhammed Bülent Akıncı, Didem Şener Dede, Bülent Yalçın
BACKGROUND: VEGF, HER2 and EGFR targeted agents are currently used in gastric, esophageal and colorectal cancers. However, treatment outcomes are still poor in most of the Gastrointestinal (GI) cancers. Immune checkpoints are one of the most promising immunotherapy approaches. In this review article, we aimed to discuss the efficacy and safety of anti-PD-1/PD-L1 therapies in GI cancers, including gastric, esophageal and colorectal cancer in the era of published or reported recent studies...
January 5, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28053544/nab-paclitaxel-as-a-potential-partner-with-checkpoint-inhibitors-in-solid-tumors
#17
REVIEW
Hatem H Soliman
Tumors recognized by the host immune system are associated with better survival. However, the immune system is often suppressed in patients with established tumor burden. Stimulating the immune system to detect and kill tumor cells has been a challenge in cancer therapy for some time. Recently, novel cancer immunotherapies, such as immune checkpoint inhibitors, monoclonal antibodies, and vaccine therapies, have emerged as promising therapeutic approaches for many solid tumors. However, for some tumors, immunotherapy alone has not provided significant benefits, and some may even be fully resistant to immunotherapy...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28052637/future-anti-hbv-strategies
#18
REVIEW
Edward J Gane
Although current oral antivirals can maintain viral suppression and reduce the risk of liver-related complications, lifelong therapy is associated with high cost, risk of breakthrough and potential toxicity. There is a need to develop a finite course of treatment which can provide sustained off-treatment virological and clinical response. The likely marker of such a clinical HBV CURE would be HBsAg clearance, but in addition cccDNA elimination would be required to prevent future reactivation (ie complete HBV cure)...
January 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28051089/cadherin-26-is-an-alpha-integrin-binding-epithelial-receptor-regulated-during-allergic-inflammation
#19
J M Caldwell, M H Collins, K A Kemme, J D Sherrill, T Wen, M Rochman, E M Stucke, L Amin, H Tai, P E Putnam, M J Jiménez-Dalmaroni, M R Wormald, A Porollo, J P Abonia, M E Rothenberg
Cadherins (CDH) mediate diverse processes critical in inflammation, including cell adhesion, migration, and differentiation. Herein, we report that the uncharacterized cadherin 26 (CDH26) is highly expressed by epithelial cells in human allergic gastrointestinal tissue. In vitro, CDH26 promotes calcium-dependent cellular adhesion of cells lacking endogenous CDHs by a mechanism involving homotypic binding and interaction with catenin family members (alpha, beta, and p120), as assessed by biochemical assays. Additionally, CDH26 enhances cellular adhesion to recombinant integrin α4β7 in vitro; conversely, recombinant CDH26 binds αE and α4 integrins in biochemical and cellular functional assays, respectively...
January 4, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28050779/a-current-perspective-on-cancer-immune-therapy-step-by-step-approach-to-constructing-the-magic-bullet
#20
REVIEW
Gabriele D'Errico, Heather L Machado, Bruno Sainz
Immunotherapy is the new trend in cancer treatment due to the selectivity, long lasting effects, and demonstrated improved overall survival and tolerance, when compared to patients treated with conventional chemotherapy. Despite these positive results, immunotherapy is still far from becoming the perfect magic bullet to fight cancer, largely due to the facts that immunotherapy is not effective in all patients nor in all cancer types. How and when will immunotherapy overcome these hurdles? In this review we take a step back to walk side by side with the pioneers of immunotherapy in order to understand what steps need to be taken today to make immunotherapy effective across all cancers...
December 2017: Clinical and Translational Medicine
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