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https://www.readbyqxmd.com/read/29047105/%C3%AE-secretase-inhibitor-reduces-immunosuppressive-cells-and-enhances-tumour-immunity-in-head-and-neck-squamous-cell-carcinoma
#1
Liang Mao, Zhi-Li Zhao, Guang-Tao Yu, Lei Wu, Wei-Wei Deng, Yi-Cun Li, Jian-Feng Liu, Lin-Lin Bu, Bing Liu, Ashok B Kulkarni, Wen-Feng Zhang, Lu Zhang, Zhi-Jun Sun
Immune evasion is a hallmark feature of cancer, and it plays an important role in tumour initiation and progression. In addition, tumour immune evasion severely hampers the desired antitumour effect in multiple cancers. In this study, we aimed to investigate the role of the Notch pathway in immune evasion in the head and neck squamous cell carcinoma (HNSCC) microenvironment. We first demonstrated that Notch1 signalling was activated in a Tgfbr1/Pten-knockout HNSCC mouse model. Notch signalling inhibition using a γ-secretase inhibitor (GSI-IX, DAPT) decreased tumour burden in the mouse model after prophylactic treatment...
October 19, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29045547/safety-of-resuming-anti-pd-1-in-patients-with-immune-related-adverse-events-iraes-during-combined-anti-ctla-4-and-anti-pd1-in-metastatic-melanoma
#2
M H Pollack, A Betof, H Dearden, K Rapazzo, I Valentine, A S Brohl, K K Ancell, G V Long, A M Menzies, Z Eroglu, D B Johnson, A N Shoushtari
Background: Combined CTLA-4 and PD-1 blockade induces high rates of immune-related adverse events (irAEs). The safety of resuming anti-PD-1 in patients who discontinue combination therapy due to irAEs is not known. Patients and Methods: We assessed patients who experienced clinically significant irAEs from combined CTLA-4 and PD-1 blockade leading to treatment discontinuation at four academic centers. We assessed the safety of resuming anti-PD-1 in terms of recurrent and distinct irAEs...
October 11, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045514/exploratory-analysis-of-the-association-of-depth-of-response-and-survival-in-patients-with-metastatic-non-small-cell-lung-cancer-treated-with-a-targeted-therapy-or-immunotherapy
#3
C E McCoach, G M Blumenthal, L Zhang, A Myers, S Tang, R Sridhara, P Keegan, R Pazdur, R C Doebele, D Kazandjian
Background: Response Evaluation Criteria in Solid Tumors (RECIST) permits rapid evaluation of new therapeutic strategies in cancer. However, RECIST does not capture the heterogeneity of response in highly active therapies. Depth of tumor response may provide a more granular view of response. We explored the association between, depth of response (DepOR), with overall survival (OS) and progression free survival (PFS) for patients with NSCLC being treated with an ALK inhibitor (ALKi) or an anti-PD-1 antibody (Ab)...
August 2, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29043842/the-protective-and-immunomodulatory-effects-of-fucoidan-against-7-12-dimethyl-benz-a-anthracene-induced-experimental-mammary-carcinogenesis-through-the-pd1-pdl1-signaling-pathway-in-rats
#4
Meilan Xue, Hui Liang, Qingjuan Tang, Chuanxing Xue, Xinjia He, Li Zhang, Zheng Zhang, Zhengyan Liang, Kang Bian, Lichen Zhang, Zhuxin Li
Fucoidan is a sulfated polysaccharide that is extracted from brown algae seaweed. This study was designed to evaluate the protective and immunomodulatory effects of dietary fucoidan on 7,12-dimethyl benz[a]anthracene (DMBA)-induced experimental mammary carcinogenesis in rats. Sixty Sprague-Dawley rats were randomly assigned to four equal groups: the control group (control group), the cancer model group (model group), and the F1 and F2 groups, which were fed fucoidan at concentrations of 200 and 400 mg/kg·body weight, respectively...
October 18, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/29043574/characterization-and-implications-of-thyroid-dysfunction-induced-by-immune-checkpoint-inhibitors-in-real-life-clinical-practice-a-long-term-prospective-study-from-a-referral-institution
#5
F Guaraldi, R La Selva, M T Samà, V D'Angelo, D Gori, P Fava, M T Fierro, P Savoia, E Arvat
PURPOSE: Autoimmune diseases are typically associated with immune checkpoints blockade. This study aims at assessing, in real-life clinical practice, the prevalence and impact of thyroid disorders induced by immune checkpoint inhibitors. METHODS: 52 patients (30 F; age 61 ± 13 years) with advanced melanoma treated with ipilimumab (3 mg/kg i.v./3 weeks; 4 doses) were included. For disease progression, 29 (16 F) of them received nivolumab (3 mg/kg i.v./2 weeks) or pembrolizumab (2 mg/kg i...
October 17, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/29038298/subversion-of-nk-cell-and-tnf-alpha-immune-surveillance-drives-tumor-recurrence
#6
Timothy Kottke, Laura Evgin, Kevin G Shim, Diana Rommelfanger, Nicolas Boisgerault, Shane Zaidi, Rosa Maria Diaz, Jill Thompson, Elizabeth Ilett, Matt Coffey, Peter Selby, Hardev Pandha, Kevin Harrington, Alan Melcher, Richard Vile
Understanding how incompletely cleared primary tumors transition from minimal residual disease (MRD) into treatment resistant, immune-invisible recurrences has major clinical significance. We show here that this transition is mediated through the subversion of two key elements of innate immune surveillance. In the first, the role of TNFalpha changes from an antitumor effector against primary tumors into a growth promoter for MRD. Second, whereas primary tumors induced a natural killer (NK)-mediated cytokine response characterized by low IL6 and elevated IFNgamma, PD-L1hi MRD cells promoted the secretion of IL6 but minimal IFNgamma, inhibiting both NK cell and T-cell surveillance...
October 15, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29031390/effects-of-postnatal-omega-3-fatty-acid-supplementation-on-offspring-pro-resolving-mediators-of-inflammation-at-6-months-and-5-years-of-age-a-double-blind-randomized-controlled-clinical-trial
#7
V H L See, E Mas, S L Prescott, L J Beilin, S Burrows, A E Barden, R C Huang, T A Mori
BACKGROUND: Resolution of inflammation is an active process involving specialised pro-resolving mediators (SPMs) generated from the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty acid supplementation during infancy may provide an intervention strategy to modify SPMs and reduce oxidative stress. This study evaluates the effect of omega-3 fatty acid supplementation in infancy on SPMs and F2-isoprostanes from 6 months to 5 years of age. METHODS: In a double-blind, placebo-controlled, parallel-group study design, 420 infants were randomized to a daily supplement of omega-3 fatty acids (280mg DHA and 110mg EPA) or olive oil (control), from birth to age 6 months...
November 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/29016938/preclinical-investigation-of-gene-mediated-cytotoxic-immunotherapy-and-checkpoint-blockade-in-glioblastoma
#8
Maria-Carmela Speranza, Carmela Passaro, Franz Ricklefs, Kazue Kasai, Sarah R Klein, Hiroshi Nakashima, Johanna K Kaufmann, Abdul-Kareem Ahmed, Michal O Nowicki, Prisca Obi, Agnieszka Bronisz, Estuardo Aguilar-Cordova, Laura K Aguilar, Brian W Guzik, Xandra Breakefield, Ralph Weissleder, Gordon J Freeman, David A Reardon, Patrick Wen, E Antonio Chiocca, Sean E Lawler
Background: Combined immunotherapy approaches are promising cancer treatments. We evaluated anti-PD-1 treatment combined with Gene-mediated cytotoxic immunotherapy (GMCI) performed by intratumoral injection of a prodrug metabolizing non-replicating adenovirus (AdV-tk), providing insitu chemotherapy and immune stimulation. Methods: The effects of GMCI on PD-L1 expression in glioblastoma were investigated in vitro and in vivo. The efficacy of the combination was investigated in two syngeneic mouse glioblastoma models (GL261 and CT-2A)...
July 24, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29016555/interleukin-10-regulated-tumour-tolerance-in-non-small-cell-lung-cancer
#9
Julius Malte Vahl, Juliane Friedrich, Susanne Mittler, Sonja Trump, Lisanne Heim, Katerina Kachler, Liubov Balabko, Nicole Fuhrich, Carol-Immanuel Geppert, Denis Iulian Trufa, Nina Sopel, Ralf Rieker, Horia Sirbu, Susetta Finotto
BACKGROUND: Lung cancer is the most life-threatening cancer type worldwide. Treatment options include surgery, radio- and chemotherapy, as well as the use of immunomodulatory antibodies. Interleukin (IL)-10 is an immunosuppressive cytokine involved in tumour immune escape. METHODS: Immunohistochemistry (IHC) on human lung surgery tissue as well as human tumour cell line cultures, FACS analysis, real-time PCR and experimental lung cancer. RESULTS: Here we discovered a positive correlation between IL-10 and IL-10 receptor (IL-10R) expression in the lung with tumour diameter in patients with lung cancer (non-small cell lung cancer), the most life-threatening cancer type worldwide...
October 10, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28994661/vitamin-d-supplementation-decreases-immune-activation-and-exhaustion-in-hiv-1-infected-youth
#10
Allison Ross Eckard, Mary Ann O'Riordan, Julia C Rosebush, Seungeun Thera Lee, Jakob G Habib, Joshua H Ruff, Danielle Labbato, Julie E Daniels, Monika Uribe-Leitz, Vin Tangpricha, Ann Chahroudi, Grace A McComsey
BACKGROUND: Heightened immune activation and exhaustion drive HIV disease progression and co-morbidities. Vitamin D has pleiotropic immunomodulatory effects, but little is known about the effects of supplementation in HIV. Our study investigates changes in immune activation and exhaustion markers after 12 months of supplementation in virologically-suppressed HIV-infected youth with vitamin D insufficiency. METHODS: This is a randomized, active-control, double-blind trial investigating with 3 different vitamin D3 doses [18,000 (standard/active-control dose), 60,000 (moderate dose) and 120,000 IU/monthly (high dose)] in 8-26 year old HIV-infected youth on combination antiretroviral therapy with baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations ≤30 ng/mL...
October 10, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28990586/immune-checkpoint-blockade-in-infectious-diseases
#11
REVIEW
Michelle N Wykes, Sharon R Lewin
The upregulation of immune checkpoint molecules, such as programmed cell death protein 1 (PD1) and cytotoxic T lymphocyte antigen 4 (CTLA4), on immune cells occurs during acute infections, such as malaria, as well as during chronic persistent viral infections, including HIV and hepatitis B virus. These pathways are important for preventing immune-driven pathology but can also limit immune-mediated clearance of the infection. The recent success of immune checkpoint blockade in cancer therapy suggests that targeting these pathways would also be effective for preventing and treating a range of infectious diseases...
October 9, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28990585/the-diverse-functions-of-the-pd1-inhibitory-pathway
#12
REVIEW
Arlene H Sharpe, Kristen E Pauken
T cell activation is a highly regulated process involving peptide-MHC engagement of the T cell receptor and positive costimulatory signals. Upon activation, coinhibitory 'checkpoints', including programmed cell death protein 1 (PD1), become induced to regulate T cells. PD1 has an essential role in balancing protective immunity and immunopathology, homeostasis and tolerance. However, during responses to chronic pathogens and tumours, PD1 expression can limit protective immunity. Recently developed PD1 pathway inhibitors have revolutionized cancer treatment for some patients, but the majority of patients do not show complete responses, and adverse events have been noted...
October 9, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28984691/intracorneal-pustular-drug-eruption-a-novel-cutaneous-adverse-event-in-anti-programmed-cell-death-1-patients-that-highlights-the-effect-of-anti-programmed-cell-death-1-in-neutrophils
#13
Cathy Yunjia Zhao, Germana Consuegra, Shaun Chou, Pablo Fernández-Peñas
The introduction of anti-programmed cell death-1 (anti-PD1) monoclonal antibodies has revolutionized the treatment of various advanced malignancies. Despite its efficacy, anti-PD1 therapy is accompanied by a variety of cutaneous adverse events. A 79-year-old man developed erythematous scaly plaques and pustules of the forehead, legs and arms after four cycles of nivolumab infusions every 2 weeks. Histology showed intracorneal pustules with dermal neutrophils and eosinophils. He was treated successfully with topical corticosteroids without discontinuation of nivolumab...
October 3, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28982616/the-yin-and-yang-of-leukotriene-b4-mediated-inflammation-in-cancer
#14
REVIEW
Venkatakrishna R Jala, Sobha R Bodduluri, Shuchismita R Satpathy, Zinal Chheda, Rajesh K Sharma, Bodduluri Haribabu
The high affinity leukotriene B4 receptor, BLT1 mediates chemotaxis of diverse leukocyte subsets to the sites of infection or inflammation. Whereas the pathological functions of LTB4/BLT1 axis in allergy, autoimmunity and cardiovascular disorders are well established; its role in cancer is only beginning to emerge. In this review, we summarize recent findings on LTB4/BLT1 axis enabling distinct outcomes toward tumor progression. In a mouse lung tumor model promoted by silicosis-induced inflammation, genetic deletion of BLT1 attenuated neutrophilic inflammation and tumor promotion...
October 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28978707/prior-dengue-virus-exposure-shapes-t-cell-immunity-to-zika-virus-in-humans
#15
Alba Grifoni, John Pham, John Sidney, Patrick H O'Rourke, Sinu Paul, Bjoern Peters, Sheridan R Martini, Aruna D de Silva, Michael J Ricciardi, Diogo M Magnani, Cassia G T Silveira, Alvino Maestri, Priscilla R Costa, Luzia Maria de-Oliveira-Pinto, Elzinandes Leal de Azeredo, Paulo Vieira Damasco, Elizabeth Phillips, Simon Mallal, Aravinda M de Silva, Matthew Collins, Anna Durbin, Sean A Diehl, Cristhiam Cerpas, Angel Balmaseda, Guillermina Kuan, Josefina Coloma, Eva Harris, James E Crowe, Mars Stone, Phillip J Norris, Michael Busch, Hector Vivanco-Cid, Josephine Cox, Barney S Graham, Julie E Ledgerwood, Lance Turtle, Tom Solomon, Esper G Kallas, David I Watkins, Daniela Weiskopf, Alessandro Sette
While progress has been made in characterizing humoral immunity to Zika virus (ZIKV) in humans, little is known regarding the corresponding T cell responses to ZIKV. Here we investigate the kinetics and viral epitopes targeted by T cells responding to ZIKV and address the critical question of whether pre-existing dengue virus (DENV) T cell immunity modulates these responses. We find that memory T cell responses elicited by prior infection with DENV or vaccination with Tetravalent Dengue Attenuated Vaccines (TDLAV) recognize ZIKV-derived peptides...
October 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28978340/ultrasound-of-the-hand-is-sufficient-to-detect-subclinical-inflammation-in-rheumatoid-arthritis-remission-a-post-hoc-longitudinal-study
#16
Hilde Berner Hammer, Tore K Kvien, Lene Terslev
BACKGROUND: Ultrasound (US) is a sensitive method for detecting joint/tendon inflammation in patients with rheumatoid arthritis (RA). Subclinical inflammation is often found in patients with RA in composite score remission. The purpose of the present study was to explore whether US of only the hands is sufficient to identify subclinical inflammation in patients with established RA in clinical remission. METHODS: A total of 209 patients with established RA (81% women, mean [SD] age 53...
October 4, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28978072/immunotherapy-of-wap-tnp-mice-with-early-stage-mammary-gland-tumors
#17
Michael Bruns, Wolfgang Deppert
The SV40 transgenic BALB/c mouse based WAP-T/WAP-TNP model for triple-negative breast cancer allows the analysis of parameters influencing immunotherapeutic approaches. Except for WAP-TNP tumors expressing the immune-dominant LCMV NP-epitope within SV40 T-antigen (T-AgNP) which is not expressed by T-Ag of WAP-T tumors, the tumors are extremely similar. Comparative anti-PD1/PD-L1 immunotherapy of WAP-T and WAP-TNP mice supported the hypothesis that the immunogenicity of tumor antigen T-cell epitopes strongly influences the success of immune checkpoint blockade therapy, with highly immunogenic T-cell epitopes favoring rapid CTL exhaustion...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28978071/analyses-of-selected-safety-endpoints-in-phase-1-and-late-phase-clinical-trials-of-anti-pd-1-and-pd-l1-inhibitors-prediction-of-immune-related-toxicities
#18
Ricardo Costa, Rubens B Costa, Sarah M Talamantes, Irene Helenoswki, Benedito A Carneiro, Young Kwang Chae, William J Gradishar, Razelle Kurzrock, Francis J Giles
PURPOSE: Anti-PD1 and PD-L1 antibodies are associated with immune-related adverse effects (irAEs). This analysis aims to assess the discrepancies between frequencies of irAEs observed in phase 1 trials with those seen in late-phase trials and to evolve the field of drug development. METHODS: PubMed search was conducted for articles published until December of 2016. Trials needed to have at least one of the study arms consisting of nivolumab, pembrolizumab or atezolizumab monotherapy...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28975832/systemic-and-adjuvant-therapies-for-intrahepatic-cholangiocarcinoma
#19
Yun Shin Chun, Milind Javle
Intrahepatic cholangiocarcinoma represents the second most common primary liver cancer and is increasing in incidence. Most patients are diagnosed at an advanced, nonsurgical stage and only about 1 in 5 cases are surgically resectable. Despite surgery, the 5-year survival is low at only 30%. Multifocal, node- or margin-positive disease is at a higher risk of recurrence after resection. There is no level 1 evidence in support of postoperative adjuvant therapy. A recent adjuvant therapy phase III trial from the Partenariat de Recherche en Oncologie Digestive-Actions Concertées dans les Cancers Colo-Rectaux et Digestifs (PRODIGE) group reported no survival advantage with adjuvant gemcitabine and oxaliplatin therapy...
July 2017: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/28968566/the-2017-complete-overhaul-of-adjuvant-therapies-for-high-risk-melanoma-and-its-consequences-for-staging-and-management-of-melanoma-patients
#20
Alexander M M Eggermont, Reinhard Dummer
The spectacular outcomes of the phase III trials regarding nivolumab versus ipilimumab in fully resected stage IIIB/C-IV and of the combination of dabrafenib (D) plus trametinib (T) in BRAF-mutant stage III patients demonstrate that effective treatments in advanced melanoma are also highly effective in the adjuvant setting. In 2016, an overall survival benefit with adjuvant high-dose ipilimumab was demonstrated, and the European Organisation for Research and Treatment of Cancer trial 1325 comparing pembrolizumab versus placebo will complete the picture in the early 2018...
September 28, 2017: European Journal of Cancer
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