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https://www.readbyqxmd.com/read/29239193/-checkpoint-inhibitors-in-the-treatment-of-upper-gastrointestinal-tract-tumors
#1
R Obermannova
Chemotherapy prolongs overall survival (OS) in esophageal (EC) and gastric cancer (GC). Unsatisfactory results of systemic therapy initiated a search for new treatment options. In metastatic disease, a number of targeted drugs were tested; however, several phase III studies assessing receptor tyrosin kinase-related signaling pathways, such as EGFR, MET/HGF or mTOR, failed. Trastuzumab remains the only targeted drug with a known molecular predictor, which extended the OS in metastatic gastric adenocarcinoma and adenocarcinoma of esophago-gastric junction...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29239191/-advances-in-immunotherapy-of-malignant-melanoma
#2
I Krajsová
Development of immunotherapy has dramatically changed poor prognosis of metastatic malignant melanoma (MM). Inhibition of immune checkpoints represents a new effective treatment. Monoclonal antibodies against CTLA-4 ipilimumab and against PD-1 (programme death 1) nivolumab and pembrolizumab prolong progression free survival and overall survival (OS) in patients with advanced metastatic MM. Both achieved significant improvement in relapse-free survival and OS also in adjuvant setting. It looks like the efficacy of the combined immunotherapy of ipilimumab with anti-PD-1 antibodies is superior to the monotherapy, but combined therapy is accompanied by higher toxicity...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29238207/advances-in-t-cell-checkpoint-immunotherapy-for-head-and-neck-squamous-cell-carcinoma
#3
REVIEW
Xinmeng Qi, Bo Jia, Xue Zhao, Dan Yu
Head and neck squamous cell carcinoma (HNSCC) has been found to be a complex group of malignancies characterized by their profound immunosuppression and high aggressiveness. In most cases of advanced HNSCC, treatment fails to obtain total cancer cure. Efforts are needed to develop new therapeutic approaches to improve HNSCC outcomes. In this light, T-cells "immune checkpoint" has attracted much attention in cancer immunotherapy. It has been broadly accepted that inhibitory T-cell immune checkpoints contribute to tumor immune escape through negative immune regulatory signals (cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4], programmed cell death 1 [PD-1], B7-H3, and B7-H4, etc)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29230210/checkpoint-blockade-toxicity-and-immune-homeostasis-in-the-gastrointestinal-tract
#4
REVIEW
Michael Dougan
Monoclonal antibodies targeting the regulatory immune "checkpoint" receptors CTLA-4, PD-1, and PD-L1 are now standard therapy for diverse malignancies including melanoma, lung cancer, and renal cell carcinoma. Although effective in many patients and able to induce cures in some, targeting these regulatory pathways has led to a new class of immune-related adverse events. In many respects, these immune toxicities resemble idiopathic autoimmune diseases, such as inflammatory bowel disease, autoimmune hepatitis, rheumatoid arthritis, and vitiligo...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29227333/illustrative-cases-for-monitoring-by-quantitative-analysis-of-braf-nras-ctdna-mutations-in-liquid-biopsies-of-metastatic-melanoma-patients-who-gained-clinical-benefits-from-anti-pd1-antibody-therapy
#5
Teofila Seremet, Simon Planken, Max Schreuer, Yanina Jansen, Mélanie Delaunoy, Hakim El Housni, Danielle Lienard, Véronique Del Marmol, Pierre Heimann, Bart Neyns
Anti-programmed death 1 (PD-1) monoclonal antibodies improve the survival of metastatic melanoma patients. Predictive or monitoring biomarkers for response to this therapy could improve the clinical management of these patients. To date, no established biomarkers are available for monitoring the response to immunotherapy. Tumor- specific mutations in circulating tumor DNA (ctDNA) such as BRAF and NRAS mutations for melanoma patients have been proposed for monitoring of immunotherapy response. We present seven illustrative cases for the use of ctDNA BRAF and NRAS mutations' monitoring in plasma...
December 8, 2017: Melanoma Research
https://www.readbyqxmd.com/read/29221649/-two-cases-of-granuloma-annulare-under-anti-pd1-therapy
#6
R Charollais, F Aubin, B Roche-Kubler, E Puzenat
BACKGROUND: Granuloma annulare as a granulomatous cutaneous reaction may be drug-induced. Immune checkpoint inhibitors including programmed death-1 (PD-1) inhibitors show remarkable antitumor activity and are approved for melanoma and other cancers. Different immune-related adverse effects have been described. We report herein a rare adverse effect of anti-PD1 therapy given for metastatic melanoma : granuloma annulare. PATIENTS AND METHODS: Two women receiving pembrolizumab metastatic melanoma presented with granuloma annulare...
December 5, 2017: Annales de Dermatologie et de Vénéréologie
https://www.readbyqxmd.com/read/29219612/nonprogression-with-avelumab-treatment-associated-with-gains-in-quality-of-life-in-metastatic-merkel-cell-carcinoma
#7
Howard L Kaufman, Matthias Hunger, Meliessa Hennessy, Michael Schlichting, Murtuza Bharmal
AIM: To assess the association between tumor response and health-related quality of life (HRQoL) in patients with metastatic Merkel cell carcinoma treated with the anti-PD-L1 avelumab. MATERIALS & METHODS: Phase II single-arm trial (NCT02155647) data of 88 patients were analyzed. Correlations between percentage reduction in tumor size and change from baseline in Functional Assessment of Cancer Therapy - General (FACT-G), FACT - Melanoma (FACT-M) and EuroQol-5 Dimension scores were calculated...
December 8, 2017: Future Oncology
https://www.readbyqxmd.com/read/29217585/patient-hla-class-i-genotype-influences-cancer-response-to-checkpoint-blockade-immunotherapy
#8
Diego Chowell, Luc G T Morris, Claud M Grigg, Jeffrey K Weber, Robert M Samstein, Vladimir Makarov, Fengshen Kuo, Sviatoslav M Kendall, David Requena, Nadeem Riaz, Benjamin Greenbaum, James Carroll, Edward Garon, David M Hyman, Ahmet Zehir, David Solit, Michael Berger, Ruhong Zhou, Naiyer A Rizvi, Timothy A Chan
CD8+ T cell-dependent killing of cancer cells requires efficient presentation of tumor antigens by human leukocyte antigen class I (HLA-I) molecules. However, the extent to which patient-specific HLA-I genotype influences response to anti-PD-1 or anti-CTLA-4 is currently unknown. We determined the HLA-I genotype of 1,535 advanced cancer patients treated with immune checkpoint blockade (ICB). Maximal heterozygosity at HLA-I loci (A, B, and C) improved overall survival after ICB compared to patients who were homozygous for at least one HLA locus...
December 7, 2017: Science
https://www.readbyqxmd.com/read/29213157/immunotherapy-and-gene-therapy-as-novel-treatments-for-cancer
#9
REVIEW
Martha Montserrat Rangel-Sosa, Estuardo Aguilar-Córdova, Augusto Rojas-Martínez
The immune system interacts closely with tumors during the disease development and progression to metastasis. The complex communication between the immune system and the tumor cells can prevent or promote tumor growth. New therapeutic approaches harnessing protective immunological mechanisms have recently shown very promising results. This is performed by blocking inhibitory signals or by activating immunological effector cells directly. Immune checkpoint blockade with monoclonal antibodies directed against the inhibitory immune receptors CTLA-4 and PD-1 has emerged as a successful treatment approach for patients with advanced melanoma...
September 30, 2017: Colombia Médica: CM
https://www.readbyqxmd.com/read/29212853/emergence-of-high-avidity-melan-a-specific-clonotypes-as-a-reflection-of-anti-pd-1-clinical-efficacy
#10
Sylvain Simon, Virginie Vignard, Emilie Varey, Tiphaine Parrot, Anne-Chantal Knol, Amir Khammari, Nadine Gervois, Francois Lang, Brigitte Dreno, Nathalie Labarriere
Therapeutic strategies using anti-PD-1-blocking antibodies reported unparalleled effectiveness for melanoma immunotherapy, but deciphering immune responses modulated by anti-PD-1 treatment remains a crucial issue. Here, we analyzed the composition and functions of the large Melan-A-specific T-cell repertoire in the peripheral blood of 9 melanoma patients before and after 2 months of treatment with anti-PD-1. We observed amplification of Melan-A-specific Vß subfamilies undetectable before therapy (thereafter called emerging Vß subfamilies) in responding patients, with a predominant expansion in patients with a complete response...
December 6, 2017: Cancer Research
https://www.readbyqxmd.com/read/29212506/chromosome-9p-copy-number-gains-involving-pd-l1-are-associated-with-a-specific-proliferation-and-immune-modulating-gene-expression-program-active-across-major-cancer-types
#11
Jan Budczies, Carsten Denkert, Balázs Győrffy, Peter Schirmacher, Albrecht Stenzinger
BACKGROUND: Inhibition of the PD-L1/PD-1 immune checkpoint axis represents one of the most promising approaches of immunotherapy for various cancer types. However, immune checkpoint inhibition is successful only in subpopulations of patients emphasizing the need for powerful biomarkers that adequately reflect the complex interaction between the tumor and the immune system. Recently, recurrent copy number gains (CNG) in chromosome 9p involving PD-L1 were detected in many cancer types including lung cancer, melanoma, bladder cancer, head and neck cancer, cervical cancer, soft tissue sarcoma, prostate cancer, gastric cancer, ovarian cancer, and triple-negative breast cancer...
December 6, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/29208646/a-serum-protein-signature-associated-with-outcome-after-anti-pd1-therapy-in-metastatic-melanoma
#12
Mario Sznol, Ryan J Sullivan, Shauna Blackmon, Genevieve Boland, Harriet M Kluger, Ruth Halaban, Antonella Bacchiocchi, Paolo A Ascierto, Marilena Capone, Carlos Oliveira, Krista Meyer, Julia Grigorieva, Senait G Asmellash, Joanna Roder, Heinrich Roder, Jeffrey S Weber
A mass spectrometry analysis was performed using serum from patients receiving checkpoint inhibitors to define baseline protein signatures associated with outcome in metastatic melanoma. Pre-treatment serum was obtained from a development set of 119 melanoma patients on a trial of nivolumab with or without a multi-peptide vaccine and from patients receiving pembrolizumab, nivolumab, ipilimumab, or both nivolumab and ipilimumab. Spectra were obtained using matrix assisted laser desorption/ionization time of flight mass spectrometry...
December 5, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29207115/current-status-and-future-prospects-of-the-strategy-of-combining-car%C3%A2-t-with-pd%C3%A2-1-blockade-for-antitumor-therapy-review
#13
Jinjing Xu, Qing Zhang, Kang Tian, Haiyu Wang, Hong Yin, Junnian Zheng
The immune system serves an important role in controlling and eradicating malignant cells. Immunotherapy for treating tumors has received much attention in recent years due to its marked effect. There are two approaches which currently lead this field: Chimeric antigen receptor‑modified T‑cell immunotherapy (CAR‑T) and programmed cell death protein-1 blockade (PD‑1 blockade). CAR‑T has emerged as a promising regimen for the treatment of a range of types of cancer, including chronic lymphoid leukemia and neuroblastoma, with studies of long term remission in certain patients...
November 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29204524/distant-intracranial-failure-in-melanoma-brain-metastases-treated-with-stereotactic-radiosurgery-in-the-era-of-immunotherapy-and-targeted-agents
#14
Sahaja Acharya, Mustafaa Mahmood, Daniel Mullen, Deshan Yang, Christina I Tsien, Jiayi Huang, Stephanie M Perkins, Keith Rich, Michael Chicoine, Eric Leuthardt, Joshua Dowling, Gavin Dunn, Jesse Keller, Clifford G Robinson, Christopher Abraham
Purpose: Stereotactic radiosurgery (SRS) in combination with immunotherapy (IMT) or targeted therapy is increasingly being used in the setting of melanoma brain metastases (MBMs). The synergistic properties of combination therapy are not well understood. We compared the distant intracranial failure rates of intact MBMs treated with SRS, SRS + IMT, and SRS + targeted therapy. Methods and materials: Combination therapy was defined as delivery of SRS within 3 months of IMT (anti-CTLA-4 /anti-PD-1 therapy) or targeted therapy (BRAF/MEK inhibitors)...
October 2017: Advances in Radiation Oncology
https://www.readbyqxmd.com/read/29195497/bilateral-uveitis-and-macular-edema-induced-by-nivolumab-a-case-report
#15
Claire Theillac, Morgane Straub, Anne-Laure Breton, Luc Thomas, Stéphane Dalle
BACKGROUND: Nivolumab is a fully human antibody which is routinely used at first therapy for metastatic melanoma. Usually, side effects are immune-related adverse events. We report a case of a man who developed bilateral anterior uveitis and macular serous retinal detachment during nivolumab treatment for metastatic melanoma. CASE PRESENTATION: A man on nivolumab treatment for a leg melanoma with duodenal and lymph nodes metastases developed a sudden bilateral visual acuity impairment and bilateral non-painfull redness eyes several days after the third infusion...
December 1, 2017: BMC Ophthalmology
https://www.readbyqxmd.com/read/29195116/pd-l1-status-does-not-predict-the-outcome-of-braf-inhibitor-therapy-in-metastatic-melanoma
#16
Katrin Schaper-Gerhardt, Steven Okoye, Rudolf Herbst, Jens Ulrich, Patrick Terheyden, Claudia Pföhler, Jochen S Utikal, Alexander Kreuter, Peter Mohr, Edgar Dippel, Imke Satzger, Antje Sucker, Dirk Schadendorf, Selma Ugurel, Ralf Gutzmer
BACKGROUND: Targeted therapies with BRAF plus MEK inhibitors (BRAFi; MEKi) represent the major treatment strategy for patients with BRAF-mutated metastatic melanoma (MM). Previous analyses suggested a correlation between programmed death-ligand 1 (PD-L1) expression in tumour tissues and the outcome of targeted therapies. This study investigated PD-L1 as a potential predictive biomarker of BRAFi-based targeted therapies in MM patients. PATIENTS AND METHODS: We analysed two independent cohorts of BRAF V600-mutated MM patients undergoing BRAFi-based therapies for PD-L1 expression in pre-treatment tumour tissues...
November 28, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29190182/checkpoint-inhibition-in-pediatric-hematologic-malignancies
#17
Kara L Davis, Archana M Agarwal, Anupam R Verma
Immune surveillance comprising of adaptive and innate immune systems is naturally designed to eliminate cancer development; overexpression of inhibitory receptors and their ligands prevent this check and lead to evasion and hence cancer progression and metastasis. The use of tumor-specific monoclonal antibodies (MAbs) targeting these checkpoint regulators is promising and has led to this novel field of cancer immunotherapy. The first antibody directed against cytotoxic T-lymphocyte associated protein 4 (CTLA-4), ipilimumab, showed promising results in clinical trials and was approved by the US Food and Drug Administration (FDA) for the treatment of metastatic melanoma in 2011...
November 30, 2017: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/29189265/development-of-a-diagnostic-programmed-cell-death-1-ligand-1-immunohistochemistry-assay-for-nivolumab-therapy-in-melanoma
#18
Therese Phillips, Molly M Millett, Xiaoling Zhang, Malinka Jansson, Rachel Cleveland, Pauline Simmons, Gregory Cherryholmes, Josette Carnahan, Josette William, Betsy Spaulding, Ilana R Satnick, H David Inzunza, Clive Taylor, John Cogswell, James Novotny, Emin Oroudjev, Henrik Winther
Nivolumab is a monoclonal antibody that blocks the interaction between programmed cell death 1 (PD1) and programmed cell death 1-ligand 1 (PD-L1), resulting in enhanced antitumor activity by the immune system. Nivolumab is currently approved by the US Food and Drug Administration (FDA) for melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma, classical Hodgkin lymphoma, squamous cell carcinoma of the head and neck, and urothelial carcinoma. PD-L1 IHC 28-8 pharmDx is FDA-approved as a complementary diagnostic for immunohistochemical (IHC) detection of PD-L1 in non-squamous NSCLC and melanoma...
October 20, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29187509/the-spectrum-incidence-kinetics-and-management-of-endocrinopathies-with-immune-checkpoint-inhibitors-for-metastatic-melanoma
#19
Emma Scott, Georgina V Long, Alexander Guminski, Roderick J Clifton-Bligh, Alexander M Menzies, Venessa Hm Tsang
OBJECTIVE: Endocrine immune related adverse events (endocrinopathies) are increasingly prevalent with the use of immune checkpoint inhibitors for the treatment of metastatic melanoma and other malignancies. There are no evidence-based guidelines for the screening or management of such patients. To describe the spectrum, incidence, kinetics, and management of endocrinopathies with immune checkpoint inhibitors. DESIGN: A prospective study conducted at Melanoma Institute Australia between April 2014 to October 2015 Methods: A total of 177 patients were treated with a) ipilimumab (N=15), b) anti-PD-1 (nivolumab, pembrolizumab) (N=103) or c) combination ipilimumab and anti-PD-1 (N=59), and were screened and managed for the subsequent endocrinopathies...
November 29, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/29187357/iap-antagonists-enhance-cytokine-production-from-mouse-and-human-inkt-cells
#20
Eleanor Clancy-Thompson, Lestat Ali, Patrick T Bruck, Mark A Exley, Richard S Blumberg, Glenn Dranoff, Michael Dougan, Stephanie K Dougan
Inhibitor of apoptosis protein (IAP) antagonists are in clinical trials for a variety of cancers, and mouse models show synergism between IAP antagonists and anti-PD-1 immunotherapy. Although IAP antagonists affect the intrinsic signaling of tumor cells, their most pronounced effects are on immune cells and the generation of antitumor immunity. Here we examined the effects of IAP antagonism on T-cell development using mouse fetal thymic organ culture and observed a selective loss of iNKT cells, an effector cell type of potential importance for cancer immunotherapy...
November 29, 2017: Cancer Immunology Research
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