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Immune checkpoint therapy

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https://www.readbyqxmd.com/read/28528510/immunogenomics-using-genomics-to-personalize-cancer-immunotherapy
#1
Rance C Siniard, Shuko Harada
While the use of genomic data has the potential to revolutionize patient care, there is still much work to be done with regard to the transformation of host-tumor interactions into favorable clinical outcomes for our patients. High-throughput technologies, such as next-generation sequencing (NGS), have rapidly advanced our understanding of oncology, and we are learning that most tumors do not simply possess consistently mutated genes that are responsible for tumorigenesis, facilitating the need for personalized cancer therapy...
May 20, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28527652/uveitis-induced-by-programmed-cell-death-protein-1-inhibitor-therapy-with-nivolumab-in-metastatic-melanoma-patient
#2
Hiroaki Kanno, Kyoko Ishida, Wataru Yamada, Takashi Nishida, Nobumichi Takahashi, Kiyofumi Mochizuki, Yuki Mizuno, Kanako Matsuyama, Tomoko Takahashi, Mariko Seishima
Nivolumab, a new immune checkpoint inhibitor, binds to programmed cell death-protein 1 receptors on T cell, blockades binding of its ligands, and augments the immunologic reaction against tumor cells. Augmented immune response, however, may lead to immune-related adverse events. Herein we describe a rare case of bilateral anterior uveitis induced by nivolumab treatment for metastatic melanoma. A 54-year-old woman presented with mild conjunctival redness and blurred vision two months after initiating nivolumab treatment...
May 17, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28525888/combination-of-desi2-and-ip10-gene-therapy-significantly-improves-therapeutic-efficacy-against-murine-carcinoma
#3
Chao Lin, HuaYing Yan, Jun Yang, Lei Li, Mei Tang, Xinyu Zhao, Chunlai Nie, Na Luo, Yuquan Wei, Zhu Yuan
DESI2 (also known as PNAS-4) is a novel pro-apoptotic gene activated during the early response to DNA damage. We previously reported that overexpression of DESI2 induces S phase arrest and apoptosis by activating checkpoint kinases. The present study was designed to test whether combination of DESI2 and IP10 could improve the therapy efficacy in vitro and in vivo. The recombinant plasmid co-expressing DESI2 and IP10 was encapsulated with DOTAP/Cholesterol nanoparticle. Immunocompetent mice bearing CT26 colon carcinoma and LL2 lung cancer were treated with the complex...
May 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525386/prognostic-value-of-kras-mutation-in-advanced-non-small-cell-lung-cancer-treated-with-immune-checkpoint-inhibitors-a-metaanalysis-and-review
#4
Jung Han Kim, Hyeong Su Kim, Bum Jun Kim
Immune checkpoint inhibitors (ICIs) have emerged as a promising treatment option in the fight against advanced non-small-cell lung cancer (NSCLC). KRAS is the most frequently mutated oncogene in NSCLC. We performed this meta-analysis to investigate if KRAS mutation status affects survival benefits of ICIs in patients with advanced NSCLC. Electronic databases were searched for eligible studies. We included randomized trials with the data of overall survival stratified by KRAS mutation status. From 3 eligible studies, 138 patients with KRAS mutant NSCLC and 371 with KRAS wild-type tumor were included in the meta-analysis...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28524159/hallmarks-of-response-to-immune-checkpoint-blockade
#5
Alexandria P Cogdill, Miles C Andrews, Jennifer A Wargo
Unprecedented advances have been made in the treatment of cancer through the use of immune checkpoint blockade, with approval of several checkpoint blockade regimens spanning multiple cancer types. However, responses to this form of therapy are not universal, and insights are clearly needed to identify optimal biomarkers of response and to combat mechanisms of therapeutic resistance. A working knowledge of the hallmarks of cancer yields insight into responses to immune checkpoint blockade, although the focus of this is rather tumour-centric and additional factors are pertinent, including host immunity and environmental influences...
May 18, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28516435/management-considerations-in-cancer-patients-with-rheumatoid-arthritis
#6
Richard J Zogala, Kristina Goutsouliak, Maria E Suarez-Almazor
Rheumatoid arthritis is a common inflammatory disease that requires treatment with immunosuppressants to control symptoms and avoid joint destruction. Managing cancer in patients with concomitant rheumatoid arthritis poses special challenges that require close coordination of care between oncologists and rheumatologists. Potential clinical issues needing special consideration include: 1) perioperative management in patients undergoing cancer surgery, which often requires discontinuation of antirrheumatic therapy; 2) use of immunosuppressant therapies for rheumatoid arthritis, especially biologic agents that inhibit cytokine and immune pathways, which conceivably could affect immune-mediated antitumor responses (the issues are different in patients with active cancer vs those with a past history of cancer and no recurrences); 3) management in the palliative care setting; and 4) use of cancer immunotherapy, such as checkpoint inhibitor agents, in patients with pre-existing rheumatoid arthritis...
May 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28516152/cdk4-6-inhibitors-in-cancer-therapy-a%C3%A2-novel-treatement-strategy-for-bladder-cancer
#7
REVIEW
Qi Pan, Anuja Sathe, Peter C Black, Peter J Goebell, Ashish M Kamat, Bernd Schmitz-Draeger, Roman Nawroth
Patients with metastatic bladder cancer (mBC) treated with cisplatin-based chemotherapy have a limited median survival of only around 14 months [1]. Despite over 30 years of basic and clinical research, until recently no therapeutic options beyond cisplatin-based therapy had entered clinical routine and, at least in the US, none of the tested agents had been approved for second-line treatment. This has changed with the advent of immune checkpoint blockade, including especially PD-1/PD-L1 inhibitors. The high response rates of 24% over a 14...
April 27, 2017: Bladder Cancer
https://www.readbyqxmd.com/read/28515940/nivolumab-induced-autoimmune-diabetes-mellitus-presenting-as-diabetic-ketoacidosis-in-a-patient-with-metastatic-lung-cancer
#8
James Luke Godwin, Shuchie Jaggi, Imali Sirisena, Pankaj Sharda, Ajay D Rao, Ranee Mehra, Colleen Veloski
BACKGROUND: Advances in cancer immunotherapy have generated encouraging results in multiple malignancies refractory to standard chemotherapies. As the use of immune checkpoint inhibitors (ICI) proliferates, the incidence of autoimmune side effects associated with these agents, termed immune related adverse events (irAE), is expected to increase. The frequency of significant irAE in ICI treated patients is about 10-20% and early recognition is critical to prevent serious morbidity and even mortality...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28515147/increased-t-cell-infiltration-elicited-by-erk5-deletion-in-a-pten-deficient-mouse-model-of-prostate-carcinogenesis
#9
Carolyn Loveridge, Ernest Mui, Rachana Patel, Ee Hong Tan, Imran Ahmad, Michelle Welsh, Julie Galbraith, Ann Hedley, Colin Nixon, Karen Blyth, Owen J Sansom, Hing Y Leung
Prostate cancer (PCa) does not appear to respond to immune checkpoint therapies where T cell infiltration may be a key limiting factor. Here we report evidence that ablating the growth regulatory kinase Erk5 can increase T cell infiltration in an established Pten-deficient mouse model of human PCa. Mice that were doubly mutant in prostate tissue for Pten and Erk5 (prostate DKO) exhibited a markedly increased median survival with reduced tumor size and proliferation compared to control Pten-mutant mice, the latter of which exhibited increased Erk5 mRNA expression...
May 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28514441/pd-1-expression-by-tumour-associated-macrophages-inhibits-phagocytosis-and-tumour-immunity
#10
Sydney R Gordon, Roy L Maute, Ben W Dulken, Gregor Hutter, Benson M George, Melissa N McCracken, Rohit Gupta, Jonathan M Tsai, Rahul Sinha, Daniel Corey, Aaron M Ring, Andrew J Connolly, Irving L Weissman
Programmed cell death protein 1 (PD-1) is an immune checkpoint receptor that is upregulated on activated T cells for the induction of immune tolerance. Tumour cells frequently overexpress the ligand for PD-1, programmed cell death ligand 1 (PD-L1), facilitating their escape from the immune system. Monoclonal antibodies that block the interaction between PD-1 and PD-L1, by binding to either the ligand or receptor, have shown notable clinical efficacy in patients with a variety of cancers, including melanoma, colorectal cancer, non-small-cell lung cancer and Hodgkin's lymphoma...
May 17, 2017: Nature
https://www.readbyqxmd.com/read/28512646/mri-in-glioma-immunotherapy-evidence-pitfalls-and-perspectives
#11
REVIEW
Domenico Aquino, Andrea Gioppo, Gaetano Finocchiaro, Maria Grazia Bruzzone, Valeria Cuccarini
Pseudophenomena, that is, imaging alterations due to therapy rather than tumor evolution, have an important impact on the management of glioma patients and the results of clinical trials. RANO (response assessment in neurooncology) criteria, including conventional MRI (cMRI), addressed the issues of pseudoprogression after radiotherapy and concomitant chemotherapy and pseudoresponse during antiangiogenic therapy of glioblastomas (GBM) and other gliomas. The development of cancer immunotherapy forced the identification of further relevant response criteria, summarized by the iRANO working group in 2015...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28512504/a-case-report-of-drug-induced-myopathy-involving-extraocular-muscles-after-combination-therapy-with-tremelimumab-and-durvalumab-for-non-small-cell-lung-cancer
#12
William Carrera, Brandon J Baartman, Gregory Kosmorsky
Recently developed anti-tumour therapies targeting immune checkpoints include tremelimumab and durvalumab. These agents have incompletely characterised side effect profiles. The authors report a 68-year-old man treated for non-small cell lung cancer (NSCLC) with a combination of tremelimumab and durvalumab. After treatment he developed diplopia, ptosis, fatigue, weakness, and an inflammatory myopathy affecting the extraocular muscles requiring hospitalisation. Electromyography (EMG) testing and muscle biopsy suggested inflammatory myopathy without sign of myasthenia...
June 2017: Neuro-ophthalmology
https://www.readbyqxmd.com/read/28512174/dynamic-changes-in-pd-l1-expression-and-immune-infiltrates-early-during-treatment-predict-response-to-pd-1-blockade-in-melanoma
#13
Ricardo E Vilain, Alexander M Menzies, James S Wilmott, Hojabr Kakavand, Jason Madore, Alexander Guminski, Elizabeth Liniker, Ben Kong, Adam Cooper, Julie R Howle, Robyn P M Saw, Valerie Jakrot, Serigne Lo, John F Thompson, Matteo S Carlino, Richard F Kefford, Georgina V Long, Richard A Scolyer
Disruption of PD-L1/cytotoxic T-cell PD-1 signalling by immune-checkpoint inhibitors improves survival in cancer patients. This study sought to identify changes in tumoral PD-L1 expression and tumor-associated immune cell flux with anti-PD1 therapies in melanoma patients, particularly early during treatment, and correlate them with treatment response<br /><br />Experimental Design: Forty-six tumor biopsies from 23 unresectable AJCC Stage III/IV melanoma patients receiving pembrolizumab/nivolumab were analyzed...
May 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28511705/pd-l1-expressing-circulating-tumour-cells-in-head-and-neck-cancers
#14
Arutha Kulasinghe, Chris Perry, Liz Kenny, Majid E Warkiani, Colleen Nelson, Chamindie Punyadeera
BACKGROUND: Blockade of the PD-1/PD-L1 immune checkpoint pathway is emerging as a promising immunotherapeutic approach for the management and treatment of head and neck cancer patients who do not respond to 1st/2nd line therapy. However, as checkpoint inhibitors are cost intensive, identifying patients who would most likely benefit from anti PD-L1 therapy is required. Developing a non-invasive technique would be of major benefit to the patient and to the health care system. CASE PRESENTATION: We report the case of a 56 year old man affected by a supraglottic squamous cell carcinoma (SCC)...
May 16, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28511092/epigenetics-and-immunotherapy-the-current-state-of-play
#15
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/28508938/immunotherapy-for-the-treatment-of-uveal-melanoma-current-status-and-emerging-therapies
#16
REVIEW
Kimberly M Komatsubara, Richard D Carvajal
PURPOSE OF REVIEW: Uveal melanoma is a distinct subset of melanoma with a biology and treatment approach that is unique from that of cutaneous melanoma. Here we will review the current data evaluating immunotherapies in both the adjuvant and metastatic settings in uveal melanoma. RECENT FINDINGS: In the adjuvant setting, interferon demonstrated no survival benefit in uveal melanoma, and studies evaluating immune-based strategies such as vaccine therapy are ongoing...
July 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28507806/preclinical-efficacy-of-immune-checkpoint-monotherapy-does-not-recapitulate-corresponding-biomarkers-based-clinical-predictions-in-glioblastoma
#17
Abhishek D Garg, Lien Vandenberk, Matthias Van Woensel, Jochen Belmans, Marco Schaaf, Louis Boon, Steven De Vleeschouwer, Patrizia Agostinis
Glioblastoma (GBM) is resistant to most multimodal therapies. Clinical success of immune-checkpoint inhibitors (ICIs) has spurred interest in applying ICIs targeting CTLA4, PD1 or IDO1 against GBM. This amplifies the need to ascertain GBM's intrinsic susceptibility (or resistance) toward these ICIs, through clinical biomarkers that may also "guide and prioritize" preclinical testing. Here, we interrogated the TCGA and/or REMBRANDT human patient-cohorts to predict GBM's predisposition toward ICIs. We exploited various broad clinical biomarkers, including mutational or predicted-neoantigen burden, pre-existing or basal levels of tumor-infiltrating T lymphocytes (TILs), differential expression of immune-checkpoints within the tumor and their correlation with particular TILs/Treg-associated functional signature and prognostic impact of differential immune-checkpoint expression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507804/hla-dependent-immune-escape-mechanisms-in-b-cell-lymphomas-implications-for-immune-checkpoint-inhibitor-therapy
#18
Marcel Nijland, Rianne N Veenstra, Lydia Visser, Chuanhui Xu, Kushi Kushekhar, Gustaaf W van Imhoff, Philip M Kluin, Anke van den Berg, Arjan Diepstra
Antigen presentation by tumor cells in the context of Human Leukocyte Antigen (HLA) is generally considered to be a prerequisite for effective immune checkpoint inhibitor therapy. We evaluated cell surface HLA class I, HLA class II and cytoplasmic HLA-DM staining by immunohistochemistry (IHC) in 389 classical Hodgkin lymphomas (cHL), 22 nodular lymphocyte predominant Hodgkin lymphomas (NLPHL), 137 diffuse large B-cell lymphomas (DLBCL), 39 primary central nervous system lymphomas (PCNSL) and 19 testicular lymphomas...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507803/pd-l1-expression-on-malignant-cells-is-no-prerequisite-for-checkpoint-therapy
#19
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/28507801/the-novel-negative-checkpoint-regulator-vista-is-expressed-in-gastric-carcinoma-and-associated-with-pd-l1-pd-1-a-future-perspective-for-a-combined-gastric-cancer-therapy
#20
Christine Böger, Hans-Michael Behrens, Sandra Krüger, Christoph Röcken
A combined blockade of V-domain Ig suppressor of T-cell activation (VISTA) and PD-1 is a promising new cancer treatment option, which was efficient in murine tumor models and is currently tested in first phase I studies. Here, we analyzed the VISTA expression in a large and well-characterized gastric cancer (GC) cohort on 464 therapy-naive GC samples and 14 corresponding liver metastases using immunohistochemistry. Staining results were correlated with clinico-pathological characteristics, genetic alterations and survival...
2017: Oncoimmunology
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