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immune-checkpoint blockers

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https://www.readbyqxmd.com/read/29600445/tumor-lysate-based-vaccines-on-the-road-to-immunotherapy-for-gallbladder-cancer
#1
REVIEW
Daniel Rojas-Sepúlveda, Andrés Tittarelli, María Alejandra Gleisner, Ignacio Ávalos, Cristián Pereda, Iván Gallegos, Fermín Eduardo González, Mercedes Natalia López, Jean Michel Butte, Juan Carlos Roa, Paula Fluxá, Flavio Salazar-Onfray
Immunotherapy based on checkpoint blockers has proven survival benefits in patients with melanoma and other malignancies. Nevertheless, a significant proportion of treated patients remains refractory, suggesting that in combination with active immunizations, such as cancer vaccines, they could be helpful to improve response rates. During the last decade, we have used dendritic cell (DC) based vaccines where DCs loaded with an allogeneic heat-conditioned melanoma cell lysate were tested in a series of clinical trials...
March 29, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29593943/tumor-immunity-landscape-in-non-small-cell-lung-cancer
#2
Xiaoqing Yu, Xuefeng Wang
Even with the great advances in immunotherapy in recent years, the response rate to immune checkpoint inhibitor therapy for non-small cell lung cancer is only about 20%. We aimed to identify new features that would better predict which patients can benefit from an immune checkpoint blocker. This study is based on the publicly available gene expression data from The Cancer Genome Atlas lung cancer samples and the newly released mutation annotation data. We performed a comprehensive analysis by correlating patient cytolytic activity index, mutational signatures, and other immune characteristics in four stratified patient groups...
2018: PeerJ
https://www.readbyqxmd.com/read/29518341/impaired-tumor-infiltrating-t-cells-in-patients-with-copd-impacts-lung-cancer-response-to-pd-1-blockade
#3
Jérôme Biton, Hanane Ouakrim, Agnès Dechartres, Marco Alifano, Audrey Mansuet-Lupo, Han Si, Rebecca Halpin, Todd Creasy, Claudie Bantsimba-Malanda, Jennifer Arrondeau, François Goldwasser, Pascaline Boudou-Rouquette, Ludovic Fournel, Nicolas Roche, Pierre-Régis Burgel, Jeremy Goc, Priyanka Devi-Marulkar, Claire Germain, Marie-Caroline Dieu-Nosjean, Isabelle Cremer, Ronald Herbst, Diane Damotte
RATIONALE: Patients with chronic obstructive pulmonary disease (COPD) have a higher prevalence of lung cancer. The chronic inflammation associated with COPD probably promotes the earliest stages of carcinogenesis. However, once tumors have progressed to malignancy, the impact of COPD on the tumor immune microenvironment remains poorly defined, and its effects on immune-checkpoint blockers' efficacy are still unknown. OBJECTIVES: To study the impact of COPD on the immune contexture of non-small cell lung cancer (NSCLC)...
March 8, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29514845/pd-1-blockade-and-cd27-stimulation-activate-distinct-transcriptional-programs-that-synergize-for-cd8-t-cell-driven-anti-tumor-immunity
#4
Sarah L Buchan, Mohannah Fallatah, Stephen M Thirdborough, Vadim Y Taraban, Anne Rogel, Lawrence J Thomas, Christine A Penfold, Li-Zhen He, Michael A Curran, Tibor Keler, Aymen Al-Shamkhani
PURPOSE: PD-1 checkpoint blockade has revolutionized the field of cancer immunotherapy, yet the frequency of responding patients is limited by inadequate T-cell priming secondary to a paucity of activatory dendritic cells (DCs). DC signals can be bypassed by CD27 agonists and we therefore investigated if the effectiveness of anti-PD-1/L1 could be improved by combining with agonist anti-CD27 monoclonal antibodies (mAb). EXPERIMENTAL DESIGN: The efficacy of PD-1/L1 blockade or agonist anti-CD27 mAb was compared with a dual-therapy approach in multiple tumor models...
March 7, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29490991/targeting-tumor-vasculature-with-tnf-leads-effector-t-cells-to-the-tumor-and-enhances-therapeutic-efficacy-of-immune-checkpoint-blockers-in-combination-with-act
#5
Angela R Elia, Matteo Grioni, Veronica Basso, Flavio Curnis, Massimo Freschi, Angelo Corti, Anna Mondino, Matteo Bellone
PURPOSE: Irregular blood flow and endothelial cell anergy, which characterize many solid tumors, hinder tumor infiltration by cytotoxic T lymphocytes (CTLs). This confers resistance to cancer immunotherapy with monoclonal antibodies directed against regulatory pathways in T lymphocytes (i.e., immune checkpoint blockade, ICB). We investigated whether NGR-TNF, a TNF derivative capable of targeting the tumor vasculature, and improving intra-tumor infiltration by activated CTLs, could sensitize tumors to ICB with antibodies specific for the PD-1 and CTLA-4 receptors...
February 28, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29485848/subcutaneous-nanodisc-vaccination-with-neoantigens-for-combination-cancer-immunotherapy
#6
Rui Kuai, Xiaoqi Sun, Wenmin Yuan, Yao Xu, Anna Schwendeman, James J Moon
While cancer immunotherapy provides new exciting treatment options for patients, there is an urgent need for new strategies that can synergize with immune checkpoint blockers and boost the patient response rates. We have developed a personalized vaccine nanodisc platform based on synthetic high-density lipoproteins for co-delivery of immunostimulatory agents and tumor antigens, including tumor-specific neoantigens. Here we examined the route of delivery, safety profiles, and therapeutic efficacy of nanodisc vaccination against established tumors...
February 27, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29485532/stat5-expression-correlates-with-recurrence-and-survival-in-melanoma-patients-treated-with-interferon-%C3%AE
#7
Devayani Machiraju, Iris Moll, Christoffer Gebhardt, Antje Sucker, Kristina Buder-Bakhaya, Dirk Schadendorf, Jessica C Hassel
Interferons (IFN) have a direct growth-inhibiting effect on tumor cells through Janus kinase-dependent activation of the transcription factor signal transducer and activator of transcription (STAT1). In vitro, signaling through STAT5 has been demonstrated to counteract this effect and lead to IFN resistance of melanoma cell lines. In 32 patients treated with IFN-α in an adjuvant setting, we investigated paraffin-embedded tumor tissue from primary melanomas and melanoma metastases for expression of STAT3 and STAT5, by immunohistochemistry, and for expression of phosphorylated signaling transduction activating transcription factor (pSTAT)3 and pSTAT5, by immunofluorescence...
February 26, 2018: Melanoma Research
https://www.readbyqxmd.com/read/29479349/adrenergic-signaling-a-targetable-checkpoint-limiting-development-of-the-antitumor-immune-response
#8
REVIEW
Guanxi Qiao, Minhui Chen, Mark J Bucsek, Elizabeth A Repasky, Bonnie L Hylander
An immune response must be tightly controlled so that it will be commensurate with the level of response needed to protect the organism without damaging normal tissue. The roles of cytokines and chemokines in orchestrating these processes are well known, but although stress has long been thought to also affect immune responses, the underlying mechanisms were not as well understood. Recently, the role of nerves and, specifically, the sympathetic nervous system, in regulating immune responses is being revealed...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29477100/diversity-of-brain-metastases-screening-and-management-in-non-small-cell-lung-cancer-in-europe-results-of-the-european-organisation-for-research-and-treatment-of-cancer-lung-cancer-group-survey
#9
Antonin Levy, Corinne Faivre-Finn, Baktiar Hasan, Eleonora De Maio, Anna S Berghoff, Nicolas Girard, Laurent Greillier, Sylvie Lantuéjoul, Mary O'Brien, Martin Reck, Anne-Marie C Dingemans, Silvia Novello, Thierry Berghmans, Benjamin Besse, Lizza Hendriks
BACKGROUND: Brain metastases (BM) are frequent in non-small cell lung cancer (NSCLC) patients, but there is a lack of evidence-based management of this patient group. We aimed to capture a snapshot of routine BM management in Europe to identify relevant research questions for future clinical trials. METHODS: An EORTC Lung Cancer Group (LCG) online survey containing questions on NSCLC BM screening and treatment was distributed between 16/02/17 and 15/06/17 to worldwide EORTC LCG members, and through several European scientific societies in the thoracic oncology field...
February 20, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29441437/immune-checkpoint-blockade-the-new-frontier-in-cancer-treatment
#10
Jeffrey M Clarke, Daniel J George, Stacey Lisi, April K S Salama
Immune checkpoint blockers have revolutionized cancer treatment in recent years. These agents are now approved for the treatment of several malignancies, including melanoma, squamous and non-squamous non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, and head and neck squamous cell carcinoma. Studies have demonstrated the significant impact of immunotherapy versus standard of care on patient outcomes, including durable response and extended survival. The use of immunotherapy-based combination therapy has been shown to further extend duration of response and survival...
February 13, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29437040/durable-clinical-benefit-in-metastatic-renal-cell-carcinoma-patients-who-discontinue-pd-1-pd-l1-therapy-for-immune-related-adverse-events
#11
Dylan J Martini, Lana Hamieh, Rana R McKay, Lauren C Harshman, Raphael Brandao, Craig K Norton, John A Steinharter, Katherine M Krajewski, Xin Gao, Fabio A Schutz, Bradley McGregor, Dominick Bossé, Aly-Khan A Lalani, Guillermo De Velasco, M Dror Michaelson, David F McDermott, Toni K Choueiri
The current standard of care for treatment of metastatic renal cell carcinoma (mRCC) patients is PD-1/PD-L1 inhibitors until progression or toxicity. Here, we characterize the clinical outcomes for 19 mRCC patients who experienced an initial clinical response (any degree of tumor shrinkage), but after immune-related adverse events (irAE) discontinued all systemic therapy. Clinical baseline characteristics, outcomes, and survival data were collected. The primary endpoint was time to progression from the date of treatment cessation (TTP)...
February 1, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29432557/epigenetic-modifiers-as-new-immunomodulatory-therapies-in-solid-tumours
#12
S Aspeslagh, D Morel, J-C Soria, S Postel-Vinay
Background: Immune therapies have revolutionized cancer treatment over the last few years by allowing improvements in overall survival. However, the majority of patients is still primary or secondary resistant to such therapies, and enhancing sensitivity to immune therapies is therefore crucial to improve patient outcome. Several recent lines of evidence suggest that epigenetic modifiers have intrinsic immunomodulatory properties, which could be of therapeutic interest. Material and Methods: We reviewed preclinical evidence and clinical studies which describe or exploit immunomodulatory properties of epigenetic agents...
February 7, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29399407/beta-blocker-use-correlates-with-better-overall-survival-in-metastatic-melanoma-patients-and-improves-the-efficacy-of-immunotherapies-in-mice
#13
Kathleen M Kokolus, Ying Zhang, Jeffrey M Sivik, Carla Schmeck, Junjia Zhu, Elizabeth A Repasky, Joseph J Drabick, Todd D Schell
Immunotherapy has expanded treatment options for cancers with historically poor outcomes, yet a significant proportion of patients still fail to achieve durable clinical benefit. We defined the contribution of β-adrenergic receptor (βAR) signaling, a component of the stress response, on success of immunotherapy for melanoma since the use of antagonists (β-blockers) is associated with improved clinical outcomes in some cancers. We show that metastatic melanoma patients who received immunotherapy had improved overall survival if they also received pan β-blockers...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399402/prognostic-relevance-of-tumor-infiltrating-lymphocytes-and-immune-checkpoints-in-pediatric-medulloblastoma
#14
Jeroen F Vermeulen, Wim Van Hecke, Elisabeth J M Adriaansen, Mieke K Jansen, Rianne G Bouma, José Villacorta Hidalgo, Paul Fisch, Roel Broekhuizen, Wim G M Spliet, Marcel Kool, Niels Bovenschen
Pediatric medulloblastomas are the most frequently diagnosed embryonal tumors of the central nervous system. Current therapies cause severe neurological and cognitive side effects including secondary malignancies. Cellular immunotherapy might be key to improve survival and to avoid morbidity. Efficient killing of tumor cells using immunotherapy requires to overcome cancer-associated strategies to evade cytotoxic immune responses. Here, we examined the immune response and immune evasion strategies in pediatric medulloblastomas...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29381418/regulatory-t-cells-tregs-a-major-immune-checkpoint-to-consider-in-combinatorial-therapeutic-hiv-1-vaccines
#15
Audrey Hubert, Nabila Seddiki
The field of immunotherapeutics is living an exceptional time as new antibodies that take brakes off T-cells and unleash them on tumours are being approved by the US-Food and Drug Administration (FDA). For the design and development of an HIV-1 therapeutic-vaccine, one would need preferably to shift the balance T-effectors/T-regulatory cells (Teff/Tregs) towards effectors to improve vaccine-specific immune-responses. Given the success with the new immune-checkpoint-blockers (ICB), it is an appropriate time for HIV-1 field to seize this opportunity and develop new therapeutic vaccine-strategies that take into consideration ICB and other immunomodulators such as cytokines...
January 30, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29372264/-lichenoid-drug-reactions
#16
REVIEW
H F Merk, L Vanstreels, M Megahed
Lichenoid drug reactions are rare compared to typical morbilliform drug exanthema or urticaria. They are associated with specific drugs or drug families like gold, antimalarial drugs, β‑blockers and angiotensin-converting-enzyme inhibitors. Recent observations included associations with novel drugs such as biologics (e. g. tumour necrosis factor antagonists) and immune checkpoint inhibitors (anti-programme cell death protein 1 antibodies). Lichenoid drug reactions most often resemble lichen planus mainly in areas of ultraviolet-light exposed skin, but also mucosal lichen planus and even bullous lesions may occur...
January 25, 2018: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
https://www.readbyqxmd.com/read/29371595/defining-the-role-of-the-tumor-vasculature-in-antitumor-immunity-and-immunotherapy
#17
REVIEW
Marco B Schaaf, Abhishek D Garg, Patrizia Agostinis
It is now well established that cancer cells co-exist within a complex environment with stromal cells and depend for their growth and dissemination on tight and plastic interactions with components of the tumor microenvironment (TME). Cancer cells incite the formation of new blood and lymphatic vessels from preexisting vessels to cope with their high nutrient/oxygen demand and favor tumor outgrowth. Research over the past decades has highlighted the crucial role played by tumor-associated blood and lymphatic vasculature in supporting immunoevasion and in subverting T-cell-mediated immunosurveillance, which are the main hallmarks of cancers...
January 25, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29336431/anti-pd1-in-the-wonder-gut-land
#18
Marie Vetizou, Giorgio Trinchieri
After the initial success of cancer immunotherapy using immune checkpoint blockers, the challenge is to understand why only a minority of patients respond to the therapy and to increase the rate of response. Three recent papers now report that the gut microbiota modulates the response to anti-PD1 therapy in patients with epithelial cancers or melanoma.
March 2018: Cell Research
https://www.readbyqxmd.com/read/29329113/therapeutic-hiv-1-vaccine-time-for-immunomodulation-and-combinatorial-strategies
#19
Nabila Seddiki, Yves Lévy
PURPOSE OF REVIEW: The purpose is to recall some of the key immunological elements that are at the crossroad and need to be combined for developing a potent therapeutic HIV-1 vaccine. RECENT FINDINGS: Therapeutic vaccines and cytokines have been commonly used to enhance and/or recall preexisting HIV-1 specific cell-mediated immune responses aiming to suppress virus replication. While the vaccine is important to stimulate HIV-1 specific T-cell responses, the cytokine may support the expansion of the stimulated virus-specific T cells...
March 2018: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29318591/immune-checkpoint-molecules-in-acute-myeloid-leukaemia-managing-the-double-edged-sword
#20
REVIEW
Willemijn Hobo, Tim J A Hutten, Nicolaas P M Schaap, Harry Dolstra
New immunotherapeutic interventions have revolutionized cancer treatment. The immune responsiveness of acute myeloid leukaemia (AML) was first demonstrated by allogeneic stem cell transplantation. In addition, milder immunotherapeutic approaches are exploited. However, the long-term efficacy of these therapies is hampered by various immune resistance and editing mechanisms. In this regard, co-inhibitory signalling pathways have been shown to play a crucial role. Via up-regulation of inhibitory checkpoints, tumour-reactive T cell and Natural Killer cell responses can be strongly impeded...
April 2018: British Journal of Haematology
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