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Cancer and immune checkpoint

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https://www.readbyqxmd.com/read/29679564/frequencies-and-expression-levels-of-programmed-death-ligand-1-pd-l1-in-circulating-tumor-rna-ctrna-in-various-cancer-types
#1
Toshiyuki Ishiba, Andreas-Claudius Hoffmann, Joshua Usher, Yahya Elshimali, Todd Sturdevant, Mai Dang, Yolanda Jaimes, Rama Tyagi, Ronald Gonzalez, Mary Grino, Jacek K Pinski, Afsaneh Barzi, Luis E Raez, Wilfried E Eberhardt, Dirk Theegarten, Heinz-Josef Lenz, Hiroyuki Uetake, Peter V Danenberg, Kathleen Danenberg
BACKGROUND: Precision medicine and prediction of therapeutic response requires monitoring potential biomarkers before and after treatment. Liquid biopsies provide noninvasive prognostic markers such as circulating tumor DNA and RNA. Circulating tumor RNA (ctRNA) in blood is also used to identify mutations in genes of interest, but additionally, provides information about relative expression levels of important genes. In this study, we analyzed PD-L1 expression in ctRNA isolated from various cancer types...
April 18, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29678394/-dermatologic-toxicities-of-immune-checkpoint-inhibitors
#2
REVIEW
V Sibaud, S Boulinguez, C Pagès, L Riffaud, L Lamant, C Chira, S Boyrie, E Vigarios, E Tournier, N Meyer
The development of immune checkpoint inhibitors (monoclonal antibodies targeting PD-1/PD-L1 or CTLA-4) represents a significant advance in the treatment of multiple cancers. Given their particular mechanism of action, which involves triggering CD4+/CD8+ T-cell activation and proliferation, they are associated with a specific safety profile. Their adverse events are primarily immune-related, and can affect practically all organs. In this context, dermatological toxicity is the most common, though it mostly remains mild to moderate and does not require discontinuation of treatment...
April 17, 2018: Annales de Dermatologie et de Vénéréologie
https://www.readbyqxmd.com/read/29678298/targeting-wnt-%C3%AE-catenin-signaling-for-cancer-immunotherapy
#3
REVIEW
Bojun Wang, Tian Tian, Karl-Henning Kalland, Xisong Ke, Yi Qu
Despite the dramatic antitumor efficiency of certain immune checkpoint inhibitors, immunotherapy has met a bottleneck regarding the response rate and resistance in cancer patients. Increasing evidence indicates that Wnt/β-catenin signaling, one of the best-characterized cancer drivers, promotes cancer progression by regulating the tumor-immune cycle in most of the nodes, including dendritic cells, T cells, and tumor cells. Specifically, abnormal Wnt/β-catenin signaling directly alters a number of regulators critical for the antitumor activities of T cells, especially effector T cells, T helper cells, and regulatory T cells...
April 17, 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/29678194/the-perfect-personalized-cancer-therapy-cancer-vaccines-against-neoantigens
#4
REVIEW
Luigi Aurisicchio, Matteo Pallocca, Gennaro Ciliberto, Fabio Palombo
In the advent of Immune Checkpoint inhibitors (ICI) and of CAR-T adoptive T-cells, the new frontier in Oncology is Cancer Immunotherapy because of its ability to provide long term clinical benefit in metastatic disease in several solid and liquid tumor types. It is now clear that ICI acts by unmasking preexisting immune responses as well as by inducing de novo responses against tumor neoantigens. Thanks to theprogress made in genomics technologies and the evolution of bioinformatics, neoantigens represent ideal targets, due to their specific expression in cancer tissue and the potential lack of side effects...
April 20, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29677240/uveal-effusion-after-immune-checkpoint-inhibitor-therapy
#5
Merina Thomas, Stephen T Armenti, M Bernadete Ayres, Hakan Demirci
Importance: Immune checkpoint inhibitors, including antiprogrammed cell death protein-1 (anti-PD-1) and antiprogrammed cell death ligand-1 (anti-PD-L1) monoclonal antibodies, have recently been introduced as a promising new immunotherapy for solid cancers. The adverse effects typically include inflammation of the skin, endocrine, and gastrointestinal systems. Objective: To describe 3 patients who developed uveal effusion after initiating anti-PD-1 and anti-PD-L1 monoclonal antibody therapy...
April 12, 2018: JAMA Ophthalmology
https://www.readbyqxmd.com/read/29675791/chemotherapy-treatment-is-associated-with-altered-pd-l1-expression-in-lung-cancer-patients
#6
Lívia Rojkó, Lilla Reiniger, Vanda Téglási, Katalin Fábián, Orsolya Pipek, Attila Vágvölgyi, László Agócs, János Fillinger, Zita Kajdácsi, József Tímár, Balázs Döme, Zoltán Szállási, Judit Moldvay
OBJECTIVES: While the predictive value of programmed cell death ligand-1 (PD-L1) protein expression for immune checkpoint inhibitor therapy of lung cancer has been extensively studied, the impact of standard platinum-based chemotherapy on PD-L1 or programmed cell death-1 (PD-1) expression is unknown. The aim of this study was to determine the changes in PD-L1 expression of tumor cells (TC) and immune cells (IC), in PD-1 expression of IC, and in the amount of stromal mononuclear cell infiltration after platinum-based chemotherapy in patients with lung cancer...
April 19, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29675465/elimination-of-established-tumors-with-nanodisc-based-combination-chemoimmunotherapy
#7
Rui Kuai, Wenmin Yuan, Sejin Son, Jutaek Nam, Yao Xu, Yuchen Fan, Anna Schwendeman, James J Moon
Although immune checkpoint blockade has shown initial success for various cancers, only a small subset of patients benefits from this therapy. Some chemotherapeutic drugs have been reported to induce antitumor T cell responses, prompting a number of clinical trials on combination chemoimmunotherapy. However, how to achieve potent immune activation with traditional chemotherapeutics in a manner that is safe, effective, and compatible with immunotherapy remains unclear. We show that high-density lipoprotein-mimicking nanodiscs loaded with doxorubicin (DOX), a widely used chemotherapeutic agent, can potentiate immune checkpoint blockade in murine tumor models...
April 2018: Science Advances
https://www.readbyqxmd.com/read/29675018/contribution-to-tumor-angiogenesis-from-innate-immune-cells-within-the-tumor-microenvironment-implications-for-immunotherapy
#8
REVIEW
Adriana Albini, Antonino Bruno, Douglas M Noonan, Lorenzo Mortara
The critical role of angiogenesis in promoting tumor growth and metastasis is strongly established. However, tumors show considerable variation in angiogenic characteristics and in their sensitivity to antiangiogenic therapy. Tumor angiogenesis involves not only cancer cells but also various tumor-associated leukocytes (TALs) and stromal cells. TALs produce chemokines, cytokines, proteases, structural proteins, and microvescicles. Vascular endothelial growth factor (VEGF) and inflammatory chemokines are not only major proangiogenic factors but are also immune modulators, which increase angiogenesis and lead to immune suppression...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29673110/programmed-death-ligand-1-expression-in-gastric-cancer-correlation-with-mismatch-repair-deficiency-and-her2-negative-status
#9
Lei Wang, Qiongyan Zhang, Shujuan Ni, Cong Tan, Xu Cai, Dan Huang, Weiqi Sheng
Gastric cancer (GC) is one of the most common malignancies. Immunotherapy is a promising targeted treatment. The immune regulatory programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis has been used as a checkpoint target for immunotherapy. Currently, considerable discrepancies exist concerning the expression status of PD-L1 and its prognostic value in GC. We aimed to evaluate the expression rates of PD-L1 in GC, and further assess its relationship with mismatch repair (MMR), and human epidermal growth factor receptor 2 (HER2) status...
April 19, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29672601/expression-of-immune-checkpoint-regulators-cytotoxic-t-lymphocyte-antigen-4-ctla-4-and-programmed-death-ligand-1-pd-l1-in-female-breast-carcinomas
#10
Ari Kassardjian, Peter I Shintaku, Neda A Moatamed
BACKGROUND: Immune checkpoint regulators, cytotoxic T lymphocyte antigen 4 (CTLA-4) and the programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) have emerged as promising new targets for cancer therapeutics. While tumor expression of PD-L1 has been shown to have objective responses to anti-PD-L1 immunotherapies, the clinical implications of CTLA-4 expression in tumor cells or immune cells in the tumor microenvironment is still controversial. We investigated the expression of CTLA-4 and PD-L1 in human breast tumors and provided a scoring system for the systematic evaluation of CTLA-4 staining...
2018: PloS One
https://www.readbyqxmd.com/read/29670880/targeting-tumor-associated-macrophages-as-a-potential-strategy-to-enhance-the-response-to-immune-checkpoint-inhibitors
#11
REVIEW
Luca Cassetta, Takanori Kitamura
Inhibition of immune checkpoint pathways in CD8+ T cell is a promising therapeutic strategy for the treatment of solid tumors that has shown significant anti-tumor effects and is now approved by the FDA to treat patients with melanoma and lung cancer. However the response to this therapy is limited to a certain fraction of patients and tumor types, for reasons still unknown. To ensure success of this treatment, CD8+ T cells, the main target of the checkpoint inhibitors, should exert full cytotoxicity against tumor cells...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29670099/nuclear-receptor-nr2f6-inhibition-potentiates-responses-to-pd-l1-pd-1-cancer-immune-checkpoint-blockade
#12
Victoria Klepsch, Natascha Hermann-Kleiter, Patricia Do-Dinh, Bojana Jakic, Anne Offermann, Mirjana Efremova, Sieghart Sopper, Dietmar Rieder, Anne Krogsdam, Gabriele Gamerith, Sven Perner, Alexandar Tzankov, Zlatko Trajanoski, Dominik Wolf, Gottfried Baier
Analyzing mouse tumor models in vivo, human T cells ex vivo, and human lung cancer samples, we provide direct evidence that NR2F6 acts as an immune checkpoint. Genetic ablation of Nr2f6, particularly in combination with established cancer immune checkpoint blockade, efficiently delays tumor progression and improves survival in experimental mouse models. The target genes deregulated in intratumoral T lymphocytes upon genetic ablation of Nr2f6 alone or together with PD-L1 blockade reveal multiple advantageous transcriptional alterations...
April 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29670088/a-cancer-vaccine-mediated-postoperative-immunotherapy-for-recurrent-and-metastatic-tumors
#13
Tingting Wang, Dangge Wang, Haijun Yu, Bing Feng, Fangyuan Zhou, Hanwu Zhang, Lei Zhou, Shi Jiao, Yaping Li
Vaccines to induce effective and sustained antitumor immunity have great potential for postoperative cancer therapy. However, a robust cancer vaccine simultaneously eliciting tumor-specific immunity and abolishing immune resistance continues to be a challenge. Here we present a personalized cancer vaccine (PVAX) for postsurgical immunotherapy. PVAX is developed by encapsulating JQ1 (a BRD4 inhibitor) and indocyanine green (ICG) co-loaded tumor cells with a hydrogel matrix. Activation of PVAX by 808 nm NIR laser irradiation significantly inhibits the tumor relapse by promoting the maturation of dendritic cells and eliciting tumor infiltration of cytotoxic T lymphocytes...
April 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29669930/tsc2-deficient-tumors-have-evidence-of-t-cell-exhaustion-and-respond-to-anti-pd-1-anti-ctla-4-immunotherapy
#14
Heng-Jia Liu, Patrick H Lizotte, Heng Du, Maria C Speranza, Hilaire C Lam, Spencer Vaughan, Nicola Alesi, Kwok-Kin Wong, Gordon J Freeman, Arlene H Sharpe, Elizabeth P Henske
Tuberous sclerosis complex (TSC) is an incurable multisystem disease characterized by mTORC1-hyperactive tumors. TSC1/2 mutations also occur in other neoplastic disorders, including lymphangioleiomyomatosis (LAM) and bladder cancer. Whether TSC-associated tumors will respond to immunotherapy is unknown. We report here that the programmed death 1 coinhibitory receptor (PD-1) is upregulated on T cells in renal angiomyolipomas (AML) and pulmonary lymphangioleiomyomatosis (LAM). In C57BL/6J mice injected with syngeneic TSC2-deficient cells, anti-PD-1 alone decreased 105K tumor growth by 67% (P < 0...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29669928/cx3cr1-identifies-pd-1-therapy-responsive-cd8-t-cells-that-withstand-chemotherapy-during-cancer-chemoimmunotherapy
#15
Yiyi Yan, Siyu Cao, Xin Liu, Susan M Harrington, Wendy E Bindeman, Alex A Adjei, Jin Sung Jang, Jin Jen, Ying Li, Pritha Chanana, Aaron S Mansfield, Sean S Park, Svetomir N Markovic, Roxana S Dronca, Haidong Dong
Although immune checkpoint inhibitors have resulted in durable clinical benefits in a subset of patients with advanced cancer, some patients who did not respond to initial anti-PD-1 therapy have been found to benefit from the addition of salvage chemotherapy. However, the mechanism responsible for the successful chemoimmunotherapy is not completely understood. Here we show that a subset of circulating CD8+ T cells expressing the chemokine receptor CX3CR1 are able to withstand the toxicity of chemotherapy and are increased in patients with metastatic melanoma who responded to chemoimmunotherapy (paclitaxel and carboplatin plus PD-1 blockade)...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29669604/confirm-a-double-blind-placebo-controlled-phase-iii-clinical-trial-investigating-the-effect-of-nivolumab-in-patients-with-relapsed-mesothelioma-study-protocol-for-a-randomised-controlled-trial
#16
Dean A Fennell, Emma Kirkpatrick, Kelly Cozens, Mavis Nye, Jason Lester, Gerard Hanna, Nicola Steele, Peter Szlosarek, Sarah Danson, Joanne Lord, Christian Ottensmeier, Daniel Barnes, Stephanie Hill, Mihalis Kalevras, Tom Maishman, Gareth Griffiths
BACKGROUND: Mesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure to asbestos and is increasing in incidence. It represents a growing health burden but remains under-researched, with limited treatment options. Early promising signals of activity relating to both PD-L1- and PD-1-targeted treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint. There is a need to evaluate checkpoint inhibitors in patients with relapsed mesothelioma where treatment options are limited...
April 18, 2018: Trials
https://www.readbyqxmd.com/read/29669262/dna-mismatch-repair-in-cancer
#17
REVIEW
Marina Baretti, Dung T Le
Microsatellite instability (MSI) refers to the hypermutator phenotype secondary to frequent polymorphism in short repetitive DNA sequences and single nucleotide substitution, as consequence of DNA mismatch repair (MMR) deficiency. MSI secondary to germline mutation in DNA MMR proteins is the molecular fingerprint of Lynch Syndrome (LS), while epigenetic inactivation of these genes is more commonly found in sporadic MSI tumors. MSI occurs at different frequencies across malignancies, although original methods to assess MSI or MMR deficiency have been developed mostly in LS related cancers...
April 15, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29669244/better-together-b7s1-checkpoint-blockade-synergizes-with-anti-pd1
#18
Melissa A Meyer, David G DeNardo
T cell checkpoint blockades can produce durable clinical responses, but only some patients and cancer types respond. In this issue of Immunity, Li et al. (2018) show B7S1-B7S1R signaling additionally regulates CD8+ T cell responses by working with the PD1-PDL1 checkpoint to block anti-tumor immunity.
April 17, 2018: Immunity
https://www.readbyqxmd.com/read/29667847/cd47-is-a-novel-potent-immunotherapy-target-in-human-malignancies-current-studies-and-future-promises
#19
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/29667757/successful-treatment-with-nivolumab-for-lung-cancer-with-low-expression-of-pd-l1-and-prominent-tumor-infiltrating-b-cells-and-immunoglobulin-g
#20
Takayuki Suyama, Yuichi Fukuda, Hiroshi Soda, Daiki Ogawara, Keisuke Iwasaki, Takuya Hara, Masataka Yoshida, Tatsuhiko Harada, Asuka Umemura, Hiroyuki Yamaguchi, Hiroshi Mukae
Little is known about the anti-tumor activity of humoral immunity in lung cancer patients treated with nivolumab, an immune checkpoint inhibitor. Herein, we report a case of lung cancer with 5% expression of PD-L1, in which a partial response to nivolumab was sustained for > 7 months. Immunohistochemical analysis of the metastatic lymph node biopsy specimen showed prominent accumulation of plasma cells and immunoglobulin G. These findings suggest that pre-existing humoral immunity may be worth considering as a candidate therapeutic biomarker of nivolumab in some lung cancer patients...
April 18, 2018: Thoracic Cancer
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