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immune-checkpoint blockade

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https://www.readbyqxmd.com/read/29666732/renal-tubular-acidosis-an-adverse-effect-of-pd-1-inhibitor-immunotherapy
#1
Sandy El Bitar, Chanudi Weerasinghe, Elie El-Charabaty, Marcel Odaimi
Immune checkpoint blockade therapy is gaining popularity among oncologists for treatment of solid and hematologic malignancies. The widespread use of these agents resulted in increasing incidence of renal immune-related adverse events. Reported renal toxicity described so far includes acute interstitial nephritis, minimal change disease, and immune complex glomerulonephritis. We report the case of a 79-year-old female with metastatic non-small cell lung cancer on anti-PD-1 therapy nivolumab. After the 4th administration of nivolumab, the treatment course was complicated with normal anion gap metabolic acidosis...
2018: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/29666026/cervical-cancer-state-of-the-science-from-angiogenesis-blockade-to-checkpoint-inhibition
#2
REVIEW
Lindsey E Minion, Krishnansu S Tewari
Vascular endothelial growth factor (VEGF) has emerged as a therapeutic target in several malignancies, including cervical cancer. Chemotherapy doublets combined with the fully humanized monoclonal antibody, bevacizumab, now constitute first-line therapy for women struggling with recurrent/metastatic cervical carcinoma. Regulatory approval for this indication was based on the phase III randomized trial, GOG 240, which demonstrated a statistically significant and clinically meaningful improvement in overall survival when bevacizumab was added to chemotherapy: 17...
March 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29664018/increased-vessel-perfusion-predicts-the-efficacy-of-immune-checkpoint-blockade
#3
Xichen Zheng, Zhaoxu Fang, Xiaomei Liu, Shengming Deng, Pei Zhou, Xuexiang Wang, Chenglin Zhang, Rongping Yin, Haitian Hu, Xiaolan Chen, Yijie Han, Yun Zhao, Steven H Lin, Songbing Qin, Xiaohua Wang, Betty Ys Kim, Penghui Zhou, Wen Jiang, Qingyu Wu, Yuhui Huang
Immune checkpoint blockade (ICB) has demonstrated curative potential in several types of cancer, but only for a small number of patients. Thus, the identification of reliable and noninvasive biomarkers for predicting ICB responsiveness is an urgent unmet need. Here, we show that ICB increased tumor vessel perfusion in treatment-sensitive EO771 and MMTV-PyVT breast tumor as well as CT26 and MCA38 colon tumor models, but not in treatment-resistant MCaP0008 and 4T1 breast tumor models. In the sensitive tumor models, the ability of anti-cytotoxic T lymphocyte-associated protein 4 or anti-programmed cell death 1 therapy to increase vessel perfusion strongly correlated with its antitumor efficacy...
April 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29663837/immune-checkpoint-blockade-in-advanced-hepatocellular-carcinoma-an-update-and-critical-review-of-ongoing-clinical-trials
#4
James J Harding
Systemic treatments for advanced hepatocellular carcinoma (HCC) are evolving rapidly and several multi-targeted tyrosine kinase inhibitors have demonstrated a survival advantage over best supportive care. Despite these treatment advances, the majority of HCC patients will progress on tyrosine kinase inhibitor therapy. Preclinical data indicate that interference with immune checkpoint molecules results in HCC growth suppression. Several clinical trials applying monoclonal antibodies to immune checkpoint molecules have demonstrated durable antitumor activity in advanced HCC patients...
April 17, 2018: Future Oncology
https://www.readbyqxmd.com/read/29662663/impact-of-antibiotic-treatment-on-immune-checkpoint-blockade-efficacy-in-advanced-non-squamous-non-small-cell-lung-cancer
#5
Florian Huemer, Gabriel Rinnerthaler, Theresa Westphal, Hubert Hackl, Georg Hutarew, Simon Peter Gampenrieder, Lukas Weiss, Richard Greil
Introduction: Despite durable responses from immune-checkpoint blockade (ICB) in a subset of patients with advanced non-small cell lung cancer (NSCLC), the majority of patients do not derive benefit from this treatment. In this analysis we evaluated the impact of concomitant administration of antibiotics during initiation of ICB on clinical outcome. Methods: Advanced non-squamous NSCLC patients receiving ICB as second- or later line between 2015 and 2017 at our tertiary cancer center in Salzburg (Austria) were included...
March 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29662550/radiotherapy-and-checkpoint-inhibitors-a-winning-new-combination
#6
REVIEW
Eric C Ko, Silvia C Formenti
Immune checkpoint blockade has recently emerged as an important therapeutic approach to the management of malignancies across multiple disease settings. Concomitantly, there has been an increasing appreciation for the role of radiotherapy in eliciting and promoting tumor-directed immune responses. In this review, we discuss the clinical evidence to date on combinations of radiotherapy with immune checkpoint inhibitors, both from the standpoint of safety and efficacy. We highlight important but yet-unanswered questions for this combination approach, as well as their implications for future prospective studies...
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
#7
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
https://www.readbyqxmd.com/read/29661225/lymphocyte-subset-expression-and-serum-concentrations-of-pd-1-pd-l1-in-sepsis-pilot-study
#8
Julie K Wilson, Yuan Zhao, Mervyn Singer, Jo Spencer, Manu Shankar-Hari
BACKGROUND: Sepsis remains a major cause of mortality in critical care, for which specific treatments are lacking. The dysregulated response to infection seen in sepsis includes features of lymphocyte dysfunction and exhaustion, suggesting that immune-stimulatory therapy may improve outcomes in certain patient groups. Monoclonal antibodies targeting checkpoint molecules, such as programmed-death 1 protein (PD-1) and its ligand PD-L1, have shown success in stimulating the immune response in patients with cancer, and are being considered for future sepsis trials...
April 17, 2018: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/29658188/strategy-to-targeting-the-immune-resistance-and-novel-therapy-in-colorectal-cancer
#9
REVIEW
Wang Gang, Jun-Jie Wang, Rui Guan, Sun Yan, Feng Shi, Jia-Yan Zhang, Zi-Meng Li, Jing Gao, Xing-Li Fu
Assessing the CRC subtypes that can predict the outcome of colorectal cancer (CRC) in patients with immunogenicity seems to be a promising strategy to develop new drugs that target the antitumoral immune response. In particular, the disinhibition of the antitumoral T-cell response by immune checkpoint blockade has shown remarkable therapeutic promise for patients with mismatch repair (MMR) deficient CRC. In this review, the authors provide the update of the molecular features and immunogenicity of CRC, discuss the role of possible predictive biomarkers, illustrate the modern immunotherapeutic approaches, and introduce the most relevant ongoing preclinical study and clinical trials such as the use of the combination therapy with immunotherapy...
April 15, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29657904/immunotherapy-for-breast-cancer-current-and-future-strategies
#10
Austin D Williams, Kyle K Payne, Avery D Posey, Christine Hill, Jose Conejo-Garcia, Carl H June, Julia Tchou
Purpose of Review: The breast tumor microenvironment is immunosuppressive and is increasingly recognized to play a significant role in tumorigenesis. A deeper understanding of normal and aberrant interactions between malignant and immune cells has allowed researchers to harness the immune system with novel immunotherapy strategies, many of which have shown promise in breast cancer. This review discusses the application of immunotherapy to the treatment of breast cancer. Recent Findings: Both basic science and clinical trial data are rapidly developing in the use of immunotherapy for breast cancer...
December 2017: Current Surgery Reports
https://www.readbyqxmd.com/read/29657128/genomic-features-of-response-to-combination-immunotherapy-in-patients-with-advanced-non-small-cell-lung-cancer
#11
Matthew D Hellmann, Tavi Nathanson, Hira Rizvi, Benjamin C Creelan, Francisco Sanchez-Vega, Arun Ahuja, Ai Ni, Jacki B Novik, Levi M B Mangarin, Mohsen Abu-Akeel, Cailian Liu, Jennifer L Sauter, Natasha Rekhtman, Eliza Chang, Margaret K Callahan, Jamie E Chaft, Martin H Voss, Megan Tenet, Xue-Mei Li, Kelly Covello, Andrea Renninger, Patrik Vitazka, William J Geese, Hossein Borghaei, Charles M Rudin, Scott J Antonia, Charles Swanton, Jeff Hammerbacher, Taha Merghoub, Nicholas McGranahan, Alexandra Snyder, Jedd D Wolchok
Combination immune checkpoint blockade has demonstrated promising benefit in lung cancer, but predictors of response to combination therapy are unknown. Using whole-exome sequencing to examine non-small-cell lung cancer (NSCLC) treated with PD-1 plus CTLA-4 blockade, we found that high tumor mutation burden (TMB) predicted improved objective response, durable benefit, and progression-free survival. TMB was independent of PD-L1 expression and the strongest feature associated with efficacy in multivariable analysis...
April 12, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29656892/cancer-germline-antigen-expression-discriminates-clinical-outcome-to-ctla-4-blockade
#12
Sachet A Shukla, Pavan Bachireddy, Bastian Schilling, Christina Galonska, Qian Zhan, Clyde Bango, Rupert Langer, Patrick C Lee, Daniel Gusenleitner, Derin B Keskin, Mehrtash Babadi, Arman Mohammad, Andreas Gnirke, Kendell Clement, Zachary J Cartun, Eliezer M Van Allen, Diana Miao, Ying Huang, Alexandra Snyder, Taha Merghoub, Jedd D Wolchok, Levi A Garraway, Alexander Meissner, Jeffrey S Weber, Nir Hacohen, Donna Neuberg, Patrick R Potts, George F Murphy, Christine G Lian, Dirk Schadendorf, F Stephen Hodi, Catherine J Wu
CTLA-4 immune checkpoint blockade is clinically effective in a subset of patients with metastatic melanoma. We identify a subcluster of MAGE-A cancer-germline antigens, located within a narrow 75 kb region of chromosome Xq28, that predicts resistance uniquely to blockade of CTLA-4, but not PD-1. We validate this gene expression signature in an independent anti-CTLA-4-treated cohort and show its specificity to the CTLA-4 pathway with two independent anti-PD-1-treated cohorts. Autophagy, a process critical for optimal anti-cancer immunity, has previously been shown to be suppressed by the MAGE-TRIM28 ubiquitin ligase in vitro...
April 6, 2018: Cell
https://www.readbyqxmd.com/read/29656492/pd-1-blockade-cellular-vesicles-for-cancer-immunotherapy
#13
Xudong Zhang, Chao Wang, Jinqiang Wang, Quanyin Hu, Benjamin Langworthy, Yanqi Ye, Wujin Sun, Jing Lin, Tianfu Wang, Jason Fine, Hao Cheng, Gianpietro Dotti, Peng Huang, Zhen Gu
Cancer cells resist to the host immune antitumor response via multiple suppressive mechanisms, including the overexpression of PD-L1 that exhausts antigen-specific CD8+ T cells through PD-1 receptors. Checkpoint blockade antibodies against PD-1 or PD-L1 have shown unprecedented clinical responses. However, limited host response rate underlines the need to develop alternative engineering approaches. Here, engineered cellular nanovesicles (NVs) presenting PD-1 receptors on their membranes, which enhance antitumor responses by disrupting the PD-1/PD-L1 immune inhibitory axis, are reported...
April 14, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29656235/effective-cancer-immunotherapy-in-mice-by-polyic-imiquimod-complexes-and-engineered-magnetic-nanoparticles
#14
Ana Isabel Bocanegra Gondan, Ane Ruiz-de-Angulo, Aintzane Zabaleta, Nina Gómez Blanco, Beatriz Macarena Cobaleda-Siles, María Jesús García-Granda, Daniel Padro, Jordi Llop, Blanca Arnaiz, María Gato, David Escors, Juan C Mareque-Rivas
Encouraging results are emerging from systems that exploit Toll like receptor (TLR) signaling, nanotechnology, checkpoint inhibition and molecular imaging for cancer immunotherapy. A major remaining challenge is developing effective, durable and tumour-specific immune responses without systemic toxicity. Here, we report a simple and versatile system based on synergistic activation of immune responses and direct cancer cell killing by combined TLR ligation using polyIC as TLR3 and imiquimod (R837) as TLR7 agonist, in combination with the model antigen ovalbumin (OVA) and phospholipid micelles loaded with zinc-doped iron oxide magnetic nanoparticles (MNPs)...
April 3, 2018: Biomaterials
https://www.readbyqxmd.com/read/29649510/ilt4-functions-as-a-potential-checkpoint-molecule-for-tumor-immunotherapy
#15
REVIEW
Aiqin Gao, Yuping Sun, Guangyong Peng
Immune checkpoint blockade therapy targeting CTLA4 and PD-1/PD-L1 is a promising strategy in the treatment of different types of cancers. However, the clinical success rates of these therapies are still moderate and varied among cancer types. Therefore, identification of alternative and novel checkpoint molecules or interrupting tolerogenic pathways is urgently needed for successful tumor immunotherapy. Immunoglobulin-like transcript 4 (ILT4) is as an immunosuppressive molecule predominantly expressed in myeloid cells, including monocytes, macrophages, dendritic cells and granulocytes...
April 9, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29648813/small-molecule-neuropilin-1-antagonists-combine-anti-angiogenic-and-anti-tumour-activity-with-immune-modulation-through-reduction-of-transforming-growth-factor-beta-tgf%C3%AE-production-in-regulatory-t-cells
#16
Jonathan Powell, Filipa Mota, David Steadman, Christelle Soudy, Jeremy T Miyauchi, Stuart Crosby, Ashley Jarvis, Tifelle Reisinge, Natalie Winfield, Graham Evans, Aled Finniear, Tamas Yelland, Yi-Tai Chou, A W Edith Chan, Andrew O'Leary, Lili Cheng, Dan Liu, Ntina Fotinou, Carla Milagre, John F Martin, Haiyan Jia, Paul Frankel, Snezana Djordjevic, Stella E Tsirka, Ian C Zachary, David L Selwood
We report the design, synthesis and comprehensive studybiological evaluation of a range ofsome potent small-molecule neuropilin-1 (NRP1) antagonists. NRP1 is implicated in the immune response to tumours, particularly in Treg cell fragility, required for PD1 checkpoint blockade. The design of these compounds was based on a previously identified compound EG00229, EG00229 which was used a starting point for optimisation. Through targeting of specific amino-acid residues additional H-bonding interactions were introduced, which led to increases in binding affinity and potency...
April 12, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29644505/cardiotoxicity-of-immunotherapy-incidence-diagnosis-and-management
#17
REVIEW
Aarti Asnani
PURPOSE OF REVIEW: This review describes cardiotoxicity associated with adoptive T cell therapy and immune checkpoint blockade. RECENT FINDINGS: Cardiotoxicity is a rare but potentially fatal complication associated with novel immunotherapies. Both affinity-enhanced and chimeric antigen receptor T cells have been reported to cause hypotension, arrhythmia, and left ventricular dysfunction, typically in the setting of cytokine release syndrome. Immune checkpoint inhibitors are generally well-tolerated but have the potential to cause myocarditis, with clinical presentations ranging from asymptomatic cardiac biomarker elevation to heart failure, arrhythmia, and cardiogenic shock...
April 11, 2018: Current Oncology Reports
https://www.readbyqxmd.com/read/29643229/t-cell-induced-csf1-promotes-melanoma-resistance-to-pd1-blockade
#18
Natalie J Neubert, Martina Schmittnaegel, Natacha Bordry, Sina Nassiri, Noémie Wald, Christophe Martignier, Laure Tillé, Krisztian Homicsko, William Damsky, Hélène Maby-El Hajjami, Irina Klaman, Esther Danenberg, Kalliopi Ioannidou, Lana Kandalaft, George Coukos, Sabine Hoves, Carola H Ries, Silvia A Fuertes Marraco, Periklis G Foukas, Michele De Palma, Daniel E Speiser
Colony-stimulating factor 1 (CSF1) is a key regulator of monocyte/macrophage differentiation that sustains the protumorigenic functions of tumor-associated macrophages (TAMs). We show that CSF1 is expressed in human melanoma, and patients with metastatic melanoma have increased CSF1 in blood compared to healthy subjects. In tumors, CSF1 expression correlated with the abundance of CD8+ T cells and CD163+ TAMs. Human melanoma cell lines consistently produced CSF1 after exposure to melanoma-specific CD8+ T cells or T cell-derived cytokines in vitro, reflecting a broadly conserved mechanism of CSF1 induction by activated CD8+ T cells...
April 11, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29629337/novel-therapeutic-targets-in-cutaneous-squamous-cell-carcinoma
#19
REVIEW
Teruki Yanagi, Shinya Kitamura, Hiroo Hata
Cutaneous squamous cell carcinoma (SCC) is one of the common cancers in Caucasians, accounting for 20-30% of cutaneous malignancies. The risk of metastasis is low in most patients; however, aggressive SCC is associated with very high mortality and morbidity. Although cutaneous SCC can be treated with surgical removal, radiation and chemotherapy singly or in combination, the prognosis of patients with metastatic SCC is poor. Recently, the usage of immune checkpoint blockades has come under consideration. To develop effective therapies that are less toxic than existing ones, it is crucial to achieve a detailed characterization of the molecular mechanisms that are involved in cutaneous SCC pathogenesis and to identify new drug targets...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29628795/the-revival-of-cpg-oligonucleotide-based-cancer-immunotherapies
#20
REVIEW
Tomasz Adamus, Marcin Kortylewski
The promising results of clinical trials using immune checkpoint inhibitors revived interests in cancer immunotherapy. However, it also became apparent that efficacy of immune checkpoint blockade can benefit from combining it with immunostimulatory strategies. Here, we review prior and re-emerging approaches using Toll-like Receptor 9 (TLR9) agonists, CpG oligodeoxynucleotides (ODNs), focused on the generation of antitumor immune responses in cancer patients. While numerous early clinical trials using TLR9 ligands in monotherapies provided evidence of CpG ODNs tolerability and safety, they failed to demonstrate sufficient antitumor efficacy...
March 2018: Contemporary Oncology Współczesna Onkologia
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