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https://www.readbyqxmd.com/read/28926891/-advances-in-immune-checkpoint-inhibitors-in-gastrointestinal-cancer
#1
X R Zhu, L Z Zheng
Currently, immunotherapy is considered as the fourth major modality of cancer treatment except surgery, chemotherapy and radiotherapy. The new therapeutic approach based on immune checkpoint inhibitors is a landmark innovation. Strategies considering checkpoint inhibitors have shown good anti-tumor effect by targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1). Moreover, DNA mismatch repair-deficient tumors appear to be potential candidates for these therapies...
September 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28926357/first-in-human-treatment-with-a-dendritic-cell-targeting-lentiviral-vector-expressing-ny-eso-1-lv305-induces-deep-durable-response-in-refractory-metastatic-synovial-sarcoma-patient
#2
Seth M Pollack, Hailing Lu, Sacha Gnjatic, Neeta Somaiah, Ryan B O'Malley, Robin L Jones, Frank J Hsu, Jan Ter Meulen
Effective induction of antitumor T cells is a pivotal goal of cancer immunotherapy. To this end, lentiviral vectors (LV) are uniquely poised to directly prime CD8 T-cell responses via transduction of dendritic cells in vivo and have shown promise as active cancer therapeutics in preclinical tumor models. However, until now, significant barriers related to production and regulation have prevented their widespread use in the clinic. We developed LV305, a dendritic cell-targeting, integration-deficient, replication incompetent LV from the ZVex platform, encoding the full-length cancer-testis antigen NY-ESO-1...
September 18, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28926356/development-of-bell-s-palsy-after-treatment-with-ipilimumab-and-nivolumab-for-metastatic-melanoma-a-case-report
#3
Julia M Zecchini, Sara Kim, Kendra Yum, Philip Friedlander
Ipilimumab is a human monoclonal antibody that targets cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and it is FDA approved for the treatment of unresectable or metastatic melanoma. Immune-related adverse events (irAEs) of gastrointestinal, dermatologic, and endocrine origin are commonly seen, ranging between 18% and 44%, with immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1/PD-L1). Rare irAEs include neurological, renal, and hematologic toxicities. Bell's palsy is a form of neurological toxicity that presents as an idiopathic paralysis of the muscles on one side of the face...
September 18, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28925793/sequential-administration-of-mva-based-vaccines-and-pd-1-pd-l1-blocking-antibodies-confers-measurable-benefits-on-tumor-growth-and-survival-preclinical-studies-with-mva-%C3%AE-gal-and-mva-muc1-tg4010-in-a-murine-tumor-model
#4
Christelle Remy-Ziller, Christine Thioudellet, Julie Hortelano, Murielle Gantzer, Virginie Nourtier, Marie-Christine Claudepierre, Benoit Sansas, Xavier Préville, Kaïdre Bendjama, Eric Quemeneur, Karola Rittner
TG4010, a Modified Vaccinia virus Ankara (MVA) expressing human mucin1 (MUC1) has demonstrated clinical benefit for patients suffering from advanced non-small cell lung cancer (NSCLC) in combination with chemotherapy. To support its development, preclinical experiments were performed with either TG4010 or β-galactosidase-encoding MVA vector (MVA-βgal) in mice presenting tumors in the lung. Tumor growth was obtained after intravenous injection of CT26 murine colon cancer cells, engineered to express either MUC1 or βgal...
September 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28925087/relationship-of-tumor-pd-l1-cd274-expression-with-lower-mortality-in-lung-high-grade-neuroendocrine-tumor
#5
Kentaro Inamura, Yusuke Yokouchi, Maki Kobayashi, Hironori Ninomiya, Rie Sakakibara, Makoto Nishio, Sakae Okumura, Yuichi Ishikawa
Programmed death-ligand 1 (PD-L1) promotes immunosuppression by binding to PD-1 on T lymphocytes. Although tumor PD-L1 expression is a potential predictive marker of clinical response to anti-PD-1/PD-L1 therapy, little is known about its association with clinicopathological features, including prognosis, in high-grade neuroendocrine tumors (HGNETs), including small-cell lung carcinoma (SCLC) and large-cell neuroendocrine carcinoma (LCNEC), of the lung. We immunohistochemically examined the membranous of expression of PD-L1 in 115 consecutive surgical cases of lung HGNET (74 SCLC cases and 41 LCNEC cases)...
September 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28923211/nivolumab-and-pembrolizumab-monoclonal-antibodies-against-programmed-cell-death-1-pd-1-that-are-interchangeable
#6
REVIEW
Vinay Prasad, Victoria Kaestner
Nivolumab (Opdivo, Bristol Meyer Squibb, New York, NY) and pembrolizumab (Keytruda, Merck, Kenilworth, NJ) are the first two US Food and Drug Administration (FDA)-approved monoclonal antibodies targeting programmed death-1 (PD-1). Nivolumab and pembrolizumab work by interfering with the interaction between PD-1 and programmed death ligand-1 (PD-L1), whose unimpeded interaction downregulates T cells allowing cancer cells to evade immune surveillance. These drugs have earned a series of FDA approvals for melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell cancer (HNSCC), urothelial cancer, classical Hodgkin lymphoma, and renal cell cancer...
April 2017: Seminars in Oncology
https://www.readbyqxmd.com/read/28923100/checkpoint-inhibitor-is-active-against-large-cell-neuroendocrine-carcinoma-with-high-tumor-mutation-burden
#7
Victoria E Wang, Anatoly Urisman, Lee Albacker, Siraj Ali, Vincent Miller, Rahul Aggarwal, David Jablons
BACKGROUND: Large cell neuroendocrine tumor (LCNEC) of the lung is a rare and aggressive tumor similar to small cell lung cancer (SCLC). Thus, it is often treated similarly to SCLC in the front-line setting with a platinum doublet. However, treatment for patients beyond the first line remains undefined. CASE PRESENTATION: We report the case of a patient with stage IB LCNEC (PD-L1 negative but positive for PD-L1 amplification and tumor mutation burden high) who progressed after adjuvant chemotherapy after surgery and subsequent therapy with an antibody drug conjugate targeting a neuroendocrine-specific cell surface marker but achieved a significant and durable response with pembrolizumab, a humanized IgG4 monoclonal anti-PD-1 antibody...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28922790/the-balance-between-cytotoxic-t-cell-lymphocytes-and-immune-checkpoint-expression-in-the-prognosis-of-colon-tumors
#8
Laetitia Marisa, Magali Svrcek, Ada Collura, Etienne Becht, Pascale Cervera, Kristell Wanherdrick, Olivier Buhard, Anastasia Goloudina, Vincent Jonchère, Janick Selves, Gerard Milano, Dominique Guenot, Romain Cohen, Chrystelle Colas, Pierre Laurent-Puig, Sylviane Olschwang, Jérémie H Lefèvre, Yann Parc, Valérie Boige, Côme Lepage, Thierry André, Jean-François Fléjou, Valentin Dérangère, François Ghiringhelli, Aurélien de Reynies, Alex Duval
Background: Immune checkpoint (ICK) expression might represent a surrogate measure of tumor-infiltrating T cell (CTL) exhaustion and therefore be a more accurate prognostic biomarker for colorectal cancer (CRC) patients than CTL enumeration as measured by the Immunoscore. Methods: The expression of ICKs, Th1, CTLs, cytotoxicity-related genes, and metagenes, including Immunoscore-like metagenes, were evaluated in three independent cohorts of CRC samples (260 microsatellite instable [MSI], 971 non-MSI)...
January 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28922567/determination-of-pd-l1-expression-in-effusions-from-mesothelioma-by-immuno-cytochemical-staining
#9
Mohammed S I Mansour, Tomas Seidal, Ulrich Mager, Amir Baigi, Katalin Dobra, Annika Dejmek
BACKGROUND: Malignant mesothelioma (MM) is an aggressive, fatal tumor. Current therapeutic options only marginally improve survival. Programmed cell death ligand 1 (PD-L1) is a dominant mediator of immunosuppression, binding to programmed cell death 1 (PD-1). PD-L1 is up-regulated in cancer cells, and the PD-1/PD-L1 pathway plays a critical role in tumor immune evasion, thus providing a target for antitumor therapy. Further, a correlation between PD-L1 expression and prognosis has been reported...
September 18, 2017: Cancer
https://www.readbyqxmd.com/read/28921638/graft-infiltrating-pd-l1-hi-cross-dressed-dendritic-cells-regulate-anti-donor-t-cell-responses-in-mouse-liver-transplant-tolerance
#10
Yoshihiro Ono, Angelica Perez-Gutierrez, Toshimasa Nakao, Helong Dai, Geoffrey Camirand, Osamu Yoshida, Shinichiro Yokota, Donna Beer Stolz, Mark A Ross, Adrian E Morelli, David A Geller, Angus W Thomson
While a key role of cross-dressing has been established in immunity to viral infection and more recently in the instigation of transplant rejection, its role in tolerance is unclear. Here, we investigated the role of intra-graft dendritic cells (DC) and cross-dressing in mouse major histocompatibility complex (MHC)-mismatched liver transplant tolerance that occurs without therapeutic immunosuppression. While donor interstitial DC diminished rapidly following transplantation, they were replaced in the liver by host DC that peaked on postoperative day (POD) 7 and persisted indefinitely...
September 16, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28920006/dosing-immunotherapy-combinations-analysis-of-3-526-patients-for-toxicity-and-response-patterns
#11
Mina Nikanjam, Harsh Patel, Razelle Kurzrock
Immunotherapy combinations are used to improve outcomes in metastatic cancer, but evidence-based knowledge of appropriate starting doses for novel combinations is lacking. Phase I-III adult combination clinical trials (≥ 1 drug was immunotherapy; anti-PD-1, PD-L1, or CTLA-4) were reviewed (PubMed Jan 1, 2010 to Sep 1, 2016; ASCO 2014-2016, ASH/ESMO 2014-2015 abstracts). The safe dose for each drug used in each combination was divided by the single-agent recommended dose to calculate dose percentage. Additive dose percentage was the sum of each dose percentage...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919992/molecular-and-clinical-characterization-of-tim-3-in-glioma-through-1-024-samples
#12
Guanzhang Li, Zheng Wang, Chuanbao Zhang, Xing Liu, Jinquan Cai, Zhiliang Wang, Huimin Hu, Fan Wu, Zhaoshi Bao, Yanwei Liu, Liang Zhao, Tingyu Liang, Fan Yang, Ruoyu Huang, Wei Zhang, Tao Jiang
Background: Researches on immunotherapy of glioma has been increasing exponentially in recent years. However, autoimmune-like side effects of current immune checkpoint blockade hindered the clinical application of immunotherapy in glioma. The discovery of the TIM-3, a tumor-specific immune checkpoint, has shed a new light on solution of this dilemma. We aimed at investigating the role of TIM-3 at transcriptome level and its relationship with clinical practice in glioma. Methods: A cohort of 325 glioma patients with RNA-seq data from Chinese Glioma Genome Atlas (CGGA project) was analyzed, and the results were well validated in TCGA RNA-seq data of 699 gliomas...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919987/programmed-death-ligand-1-pd-l1-expression-influences-the-immune-tolerogenic-microenvironment-in-antiretroviral-therapy-refractory-kaposi-s-sarcoma-a-pilot-study
#13
Salvinia Mletzko, David J Pinato, Rebecca C Robey, Alessia Dalla Pria, Peter Benson, Nesrina Imami, Mark Bower
Upregulation of programmed death ligand 1 (PD-L1) is a mechanism of immune escape utilized by a variety of tumors. PD-L1 expression in tumor cells or in the surrounding infiltrate correlates with clinical responsiveness to novel therapies targeting the PD-1/PD-L1 immune checkpoint. In the context of HIV-1 infection, Kaposi's sarcoma (KS) is largely responsive to restoration of immunity following combination antiretroviral therapy (cART), but there is a subset that is not. We hypothesized that this subset of cART-refractory KS may utilize the PD-L1 pathway of immune escape...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28918474/induction-of-immunogenic-cell-death-in-lymphoma-cells-by-wharton-s-jelly-mesenchymal-stem-cell-conditioned-medium
#14
Daniel Hao Lin, Arijit Biswas, Mahesh Choolani, Chui-Yee Fong, Ariff Bongso
Strategies that induce immunogenic cell death (ICD) or downregulate CD47 or PD-L1 expression have resulted in successful therapeutic options for tumor eradication. Several groups have reported the tumoricidal effects of human umbilical cord Wharton's jelly stem cells (hWJSCs) or its conditioned medium (hWJSC-CM) on certain cancers but the mechanisms have not been elucidated. Since hWJSCs possess immunomodulatory properties, we investigated whether one of the tumoricidal mechanisms was via ICD. We first concentrated hWJSC-CM into a 3 kDa concentrate and then exposed various concentrations of this concentrate to human lymphoma cells to find out which concentration had the greatest tumoricidal effect...
September 16, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28916815/programmed-death-ligand-1-pd-l1-expression-in-tumour-cell-and-tumour-infiltrating-lymphocytes-of-her2-positive-breast-cancer-and-its-prognostic-value
#15
Ahrong Kim, So Jeong Lee, Young Keum Kim, Won Young Park, Do Youn Park, Jee Yeon Kim, Chang Hun Lee, Gyungyub Gong, Gi Yeong Huh, Kyung Un Choi
Immunotherapy targeting PD-1/PD-L1 axis showed benefits in cancer. Prognostic significance of tumour infiltrating lymphocytes (TILs) has been determined. We evaluated PD-L1 protein expression in tumour cells and TILs, PD-L1 mRNA level and various histopathologic factors including TILs using 167 formalin-fixed paraffin embedded tissues and 39 fresh tissue of HER2-positive breast cancer. TILs level and PD-L1 expression in tumour cells and TILs were significantly correlated one another. PD-L1 positivity in tumour cells was associated with high histologic grade and high TILs level (p < 0...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916658/t-cells-deficient-in-diacylglycerol-kinase-%C3%AE-are-resistant-to-pd-1-inhibition-and-help-create-persistent-host-immunity-to-leukemia
#16
Weiqing Jing, Jill Alane Gershan, Sandra Holzhauer, James Weber, Katie Palen, Laura McOlash, Kirthi Pulakanti, Erin Wesley, Sridhar Rao, Bryon D Johnson, Matthew J Riese
Efforts to improve the efficacy of adoptive T cell therapies and immune checkpoint therapies in myelogenous leukemia are desired. In this study, we evaluated the anti-leukemia activity of adoptively transferred polyclonal cancer antigen-reactive T cells deficient in the regulator diacylglycerol kinase-zeta (DGKζ) with or without PD-1/PD-L1 blockade. In the C1498 mouse model of myeloid leukemia, we showed that leukemia was eradicated more effectively in DGKζ-deficient (DGKζ-/-) mice than wild-type mice. T cells transferred from DGKζ-deficient mice to wild-type tumor-bearing recipients conferred this benefit...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28916112/a-novel-mimovirus-encoding-chga10-19-peptide-with-pd-l1-induces-t-cell-tolerance-and-ameliorates-the-severity-of-diabetes
#17
Hong Sun, Xiaoguang Han, Xiuhui Yan, Jingli Xu, Qiujing Huang, Fanqing Meng, Hongjin Zhang, Shufa Li
Related studies demonstrate that type 1 diabetes (T1D) is caused by β-cell antigen specific autoreactive CD8+ T cells. ChgA has recently been identified as the autoantigen in NOD mice and T1D patients. Therefore, attenuating the activation of ChgA specific CD8+ T cells might be a promising target for T1D therapy. The negative co-stimulatory PD-L1 inhibits T cell mediated alloimmunity and induces tolerance. In this experiment, a novel mimovirus encoding ChgA10-19 peptide with PD-L1 was constructed. The NOD...
September 7, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28915720/pseudoprogression-in-microsatellite-instability-high-colorectal-cancer-during-treatment-with-combination-t-cell-mediated-immunotherapy-a-case-report-and-literature-review
#18
Young Kwang Chae, Si Wang, Halla Nimeiri, Aparna Kalyan, Francis J Giles
Evading tumor-mediated immunosuppression through antibodies to immune checkpoints has shown clinical benefit in patients with select solid tumors. There is a heterogeneity of responses in patients receiving immunotherapy, including pseudoprogression in which the tumor burden increases initially before decreasing to reach disease control. The characteristics and basis of pseudoprogression, however, remains poorly understood. We hereby report a case of microsatellite instability (MSI)-high metastatic colorectal cancer treated with combination of OX40 agonist and programmed death ligand-1 (PD-L1) antagonist that demonstrated pseudoprogression reaching 163% increase from baseline tumor burden...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915714/the-efficacy-of-anti-pd-1-pd-l1-therapy-and-its-comparison-with-egfr-tkis-for-advanced-non-small-cell-lung-cancer
#19
REVIEW
Zhixin Sheng, Xu Zhu, Yanhua Sun, Yanxia Zhang
PURPOSE: To better understand the efficacy and safety of anti-PD-1/PD-L1 therapy (atezolizumab, pembrolizumab, nivolumab) in patients with previously treated advanced non-small-cell lung cancer (NSCLC). METHODS: The Cochrane Controlled Trial Register, Embase, Medline, and the Science Citation Index were searched for prospective published reports of atezolizumab, pembrolizumab, nivolumab in previously treated patients with advanced NSCLC. RESULTS: Finally, we identified 14 prospective published reports including four trials of atezolizumab covering 542 subjects, three trials of pembrolizumab covering 1566 subjects, seven trials of nivolumab covering 1678 subjects...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914717/the-relationship-between-mismatch-repair-deficiency-and-pd-l1-expression-in-breast-carcinoma
#20
Anne M Mills, Erik A Dill, Christopher A Moskaluk, Jaroslaw Dziegielewski, Tim N Bullock, Patrick M Dillon
Mismatch repair (MMR) deficiency in solid tumors has recently been linked to susceptibility to immunotherapies targeting the programmed cell death-1 (PD-1)/programmed cell death-1 ligand (PD-L1) axis. Loss of MMR proteins has been shown to correlate with tumoral PD-L1 expression in colorectal and endometrial carcinomas, but the association between expression of MMR proteins and PD-L1 has not previously been studied in breast carcinoma, where MMR deficiency is less common. We assessed the relationship between PD-L1 and MMR protein expression by immunohistochemistry in 245 primary and 40 metastatic breast carcinomas...
September 13, 2017: American Journal of Surgical Pathology
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