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https://www.readbyqxmd.com/read/29775689/biomarkers-for-checkpoint-inhibition-in-hematologic-malignancies
#1
REVIEW
Djordje Atanackovic, Tim Luetkens
In the past few years we have seen remarkable paradigm shifts in the treatment of many solid tumors due to the introduction of inhibitors targeting immune checkpoints such as PD-1/PD-L1 and CTLA-4. Recent results indicate that checkpoint inhibition also represents a very promising approach for certain types of hematologic malignancies. Unfortunately, treatment with checkpoint inhibitors is also associated with substantial toxicities and high costs and only a subset of patients appears to derive clinical benefit from these treatments...
May 15, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29771573/increased-circulating-proinflammatory-t-lymphocytes-in-children-with-different-forms-of-anterior-uveitis-results-from-a-pilot-study
#2
Karoline Walscheid, Lisa Neekamp, Arnd Heiligenhaus, Toni Weinhage, Carsten Heinz, Dirk Foell
PURPOSE: To characterize peripheral blood T cells in juvenile idiopathic arthritis-associated uveitis (JIAU). METHODS: Blood samples were taken from children with JIAU (n = 18), JIA without ocular involvement (n = 11), idiopathic anterior uveitis (IAU, n = 12), and healthy controls (n = 11). Cells were stained for T cell surface markers, and intracellular cytokine staining was performed after cell stimulation and analyzed by flow cytometry. RESULTS: The Th1/Th2 ratio was increased in JIAU patients...
May 17, 2018: Ocular Immunology and Inflammation
https://www.readbyqxmd.com/read/29769383/incidence-of-thyroid-function-test-abnormalities-in-patients-receiving-immune-checkpoint-inhibitors-for-cancer-treatment
#3
Nisha Subhash Patel, Anais Oury, Gregory A Daniels, Lyudmila Bazhenova, Sandip Pravin Patel
BACKGROUND: With the advent of immune-checkpoint inhibitor (ICI) therapy (anti-CTLA-4, anti-PD-1), immune-related adverse events such as thyroid function test abnormalities (TFTAs) are common, with a reported incidence range of 2%-15% depending upon the ICI used. The aim of this study is to describe the incidence of TFTAs retrospectively in patients who received ICI therapy. METHODS: A total of 285 patients were reviewed (178 male, 107 female; 16-94 years of age), of whom 218 had no baseline TFTAs, 61 had baseline TFTAs, and 6 had a history of thyroidectomy (excluded)...
May 16, 2018: Oncologist
https://www.readbyqxmd.com/read/29769249/spatial-distribution-and-function-of-t-follicular-regulatory-cells-in-human-lymph-nodes
#4
Ismail Sayin, Andrea J Radtke, Laura A Vella, Wenjie Jin, E John Wherry, Marcus Buggert, Michael R Betts, Ramin S Herati, Ronald N Germain, David H Canaday
T follicular regulatory (Tfr) cells are a population of CD4+ T cells that express regulatory T cell markers and have been shown to suppress humoral immunity. However, the precise mechanisms and location of Tfr-mediated suppression in the lymph node (LN) microenvironment are unknown. Using highly multiplexed quantitative imaging and functional assays, we examined the spatial distribution, suppressive function, and preferred interacting partners of Tfr cells in human mesenteric LNs. We find that the majority of Tfr cells express low levels of PD-1 and reside at the border between the T cell zone and B cell follicle, with very few found in the germinal centers (GCs)...
May 16, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29769148/current-landscape-and-future-of-dual-anti-ctla4-and-pd-1-pd-l1-blockade-immunotherapy-in-cancer-lessons-learned-from-clinical-trials-with-melanoma-and-non-small-cell-lung-cancer-nsclc
#5
REVIEW
Young Kwang Chae, Ayush Arya, Wade Iams, Marcelo R Cruz, Sunandana Chandra, Jaehyuk Choi, Francis Giles
Immunotherapy is among the most rapidly evolving treatment strategies in oncology. The therapeutic potential of immune-checkpoint inhibitors is exemplified by the recent hail of Food and Drug Administration (FDA) approvals for their use in various malignancies. Continued efforts to enhance outcomes with immunotherapy agents have led to the formulation of advanced treatment strategies. Recent evidence from pre-clinical studies evaluating immune-checkpoint inhibitors in various cancer cell-lines has suggested that combinatorial approaches may have superior survival outcomes compared to single-agent immunotherapy regimens...
May 16, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29769011/evolving-strategies-for-the-treatment-of-t-cell-lymphoma-a-systematic-review-and-recent-patents
#6
Kamel Laribi, Mustapha Alani, Catherine Truong, Alix Baugier de Materre
OBJECTIVE: Mature T-cell lymphomas are a heterogeneous group of T-cell malignancies with a poor outcome. The discovery of new molecular biomarkers has led to the emergence of new drugs in recent years that target various signaling pathways. METHOD: We examined all pertinent published patents through 2015 that analyzed novel methods for the diagnosis and treatment of T cell lymphoma, as well as related published and unpublished studies. Selection criteria were established before data collection...
May 16, 2018: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/29757670/regulatory-t-cell-dynamics-with-abatacept-treatment-in-rheumatoid-arthritis
#7
Kane Langdon, Nagaraja Haleagrahara
The progressive damage in rheumatoid arthritis (RA) has been linked to an increase in inflammatory Th1/Th17 cells and a decrease in number or function of immunomodulatory regulatory T cells (Tregs). Many therapies that are effective in RA are shown to affect Th1/Th17 cells and/or Tregs. One such therapy, abatacept, utilizes a physiologic immunomodulatory molecule called cytotoxic lymphocyte antigen-4 (CTLA-4) which causes contact-dependent inhibition of inflammatory T-cell activation. Recent advances in CTLA-4 research has uncovered the method by which this occurs physiologically but the actions of the CTLA-4Ig fusion protein are still not fully understood...
May 14, 2018: International Reviews of Immunology
https://www.readbyqxmd.com/read/29755699/sequential-immunotherapy-in-a-patient-with-primary-refractory-hodgkin-lymphoma-and-novel-mutations
#8
Richard Greil, Lisa Pleyer, Bettina Jansko, Carmen Feierabend, Lukas Rettenbacher, Olga Stiefel, Christoph Rass, Patrick Morre, Daniel Neureiter, Sigrun Greil-Ressler
Primary resistant Hodgkin lymphoma is an aggressive disease with few treatment options and short survival. Neoplastic cells of classical Hodgkin lymphoma are heavily dependent on microenvironmental stimuli, regularly express PD-L1, and a relevant proportion of relapsed patients is sensitive to blocking of the PD1/PD-L1 axis. However, response duration is limited and further treatment options are unknown but urgently needed. We report a case of a patient without relevant response to five subsequent chemotherapy regimens who immediately and dramatically responded to an anti-PD1 mab...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29750753/immune-checkpoint-inhibitor-anti-ctla-4-anti-pd-1-therapy-alone-versus-immune-checkpoint-inhibitor-anti-ctla-4-anti-pd-1-therapy-in-combination-with-anti-rankl-denosumuab-in-malignant-melanoma-a-retrospective-analysis-at-a-tertiary-care-center
#9
Muhammad Z Afzal, Keisuke Shirai
Denosumab is a monoclonal antibody against RANK ligand with a role in the prevention of skeletal-related events and is also known to possess antitumor properties. In this retrospective review, we aim to evaluate the synergist effect of a combination therapy with immune checkpoint inhibitors and denosumab in malignant melanoma patients. Patients of 18 years of age or older with a diagnosis of malignant melanoma who have received immune checkpoint inhibitors and denosumab between June 2015 and May 2017 were divided into two cohorts: cohort A (immune checkpoint inhibitors only) and cohort B (immune checkpoint inhibitors and denosumab)...
May 10, 2018: Melanoma Research
https://www.readbyqxmd.com/read/29750176/adoptive-cell-therapy-with-tumor-infiltrating-lymphocytes-in-advanced-melanoma-patients
#10
Mélanie Saint-Jean, Anne-Chantal Knol, Christelle Volteau, Gaëlle Quéreux, Lucie Peuvrel, Anabelle Brocard, Marie-Christine Pandolfino, Soraya Saiagh, Jean-Michel Nguyen, Christophe Bedane, Nicole Basset-Seguin, Amir Khammari, Brigitte Dréno
Immunotherapy for melanoma includes adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TILs). This monocenter retrospective study was undertaken to evaluate the efficacy and safety of this treatment of patients with advanced melanoma. All advanced melanoma patients treated with TILs using the same TIL expansion methodology and same treatment interleukin-2 (IL-2) regimen between 2009 and 2012 were included. After sterile intralesional excision of a cutaneous or subcutaneous metastasis, TILs were produced according to a previously described method and then infused into the patient who also received a complementary subcutaneous IL-2 regimen...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29748391/tumor-specific-inhibition-of-in-situ-vaccination-by-distant-untreated-tumor-sites
#11
Zachary S Morris, Emily I Guy, Lauryn R Werner, Peter M Carlson, Clinton M Heinze, Jasdeep S Kler, Sara M Busche, Abigail A Jaquish, Raghava N Sriramaneni, Lakeesha Carmichael, Hans Loibner, Stephen D Gillies, Alan J Korman, Amy K Erbe, Jacquelyn A Hank, Alexander L Rakhmilevich, Paul M Harari, Paul M Sondel
In situ vaccination is an emerging cancer treatment strategy that uses local therapies to stimulate a systemic antitumor immune response. We previously reported an in situ vaccination effect when combining radiation (RT) with intra-tumor (IT) injection of tumor-specific immunocytokine (IC), a fusion of tumor-specific antibody and IL2 cytokine. In mice bearing two tumors, we initially hypothesized that delivering RT plus IT-IC to the "primary" tumor would induce a systemic antitumor response causing regression of the "secondary" tumor...
May 10, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29743521/e2f1-inhibition-mediates-cell-death-of-metastatic-melanoma
#12
Florian Rouaud, Nedra Hamouda-Tekaya, Michaël Cerezo, Patricia Abbe, Joséphine Zangari, Veronique Hofman, Mickaël Ohanna, Baharia Mograbi, Najla El-Hachem, Zohra Benfodda, Alexandre Lebeau, Meri K Tulic, Paul Hofman, Corine Bertolotto, Thierry Passeron, Jean-Sébastien Annicotte, Robert Ballotti, Stéphane Rocchi
Melanoma is one of the most lethal cancers when it reaches a metastatic stage. Despite advancements in targeted therapies (BRAF inhibitors) or immunotherapies (anti-CTLA-4 or anti-PD1), most patients with melanoma will need additional treatment. Thus, there is an urgent need to develop new therapeutical approaches to bypass resistance and achieve more prolonged responses. In this context, we were interested in E2F1, a transcription factor that plays a major role in the control of cell cycle under physiological and pathological conditions...
May 9, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29743050/unmasking-of-intracranial-metastatic-melanoma-during-ipilimumab-nivolumab-therapy-case-report-and-literature-review
#13
Marin A McDonald, Parag Sanghvi, Julie Bykowski, Gregory A Daniels
BACKGROUND: While data from several studies over the last decade has demonstrated that introduction of immunologic checkpoint blockage therapy with anti-CTLA-4/PD-1 drugs leads to improved survival in metastatic melanoma patients, relatively little is known about brain-specific therapeutic response and adverse events in the context of immunotherapeutic treatment of intracranial disease. Here we report two independent cases of new intracranial metastases presenting after initiation of combined checkpoint blockade Ipilimumab and Nivolumab for recurrent metastatic melanoma in the context of positive systemic disease response...
May 9, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29740718/combination-immunotherapy-in-non-small-cell-lung-cancer
#14
REVIEW
Melina E Marmarelis, Charu Aggarwal
PURPOSE OF REVIEW: Checkpoint blockade has changed the treatment landscape in non-small cell lung cancer (NSCLC), but single-agent approaches are effective for only a select subset of patients. Here, we will review the evidence for combination immunotherapies in NSCLC and the clinical data evaluating the efficacy of this approach. RECENT FINDINGS: Clinical trials evaluating combination PD-1 and CTLA-4 blockade as well as PD-1 in combination with agents targeting IDO1, B7-H3, VEGF, and EGFR show promising results...
May 8, 2018: Current Oncology Reports
https://www.readbyqxmd.com/read/29735917/cancer-immunotherapy-a-focus-on-the-regulation-of-immune-checkpoints
#15
REVIEW
Tao Shi, Yanyu Ma, Lingfeng Yu, Jiaxuan Jiang, Sunan Shen, Yayi Hou, Tingting Wang
In recent years, the role of cancer immunotherapy has become increasingly important compared to traditional cancer treatments, including surgery, chemotherapy and radiotherapy. Of note, the clinical successes of immune checkpoint blockade, such as PD-1 and CTLA-4, represent a landmark event in cancer immunotherapy development. Therefore, further exploration of how immune checkpoints are regulated in the tumor microenvironment will provide key insights into checkpoint blockade therapy. In this review, we discuss in details about the regulation of immune checkpoints mediated by immune cells, oncolytic viruses, epigenetics, and gut microbiota and mutual regulation by co-expressed checkpoints...
May 7, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29735668/modeling-combination-therapy-for-breast-cancer-with-bet-and-immune-checkpoint-inhibitors
#16
Xiulan Lai, Andrew Stiff, Megan Duggan, Robert Wesolowski, William E Carson, Avner Friedman
CTLA-4 is an immune checkpoint expressed on active anticancer T cells. When it combines with its ligand B7 on dendritic cells, it inhibits the activity of the T cells. The Bromo- and Extra-Terminal (BET) protein family includes proteins that regulate the expression of key oncogenes and antiapoptotic proteins. BET inhibitor (BETi) has been shown to reduce the expression of MYC by suppressing its transcription factors and to down-regulate the hypoxic transcriptome response to VEGF-A. This paper develops a mathematical model of the treatment of cancer by combination therapy of BETi and CTLA-4 inhibitor...
May 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29735366/self-delivering-rnai-targeting-pd-1-improves-tumor-specific-t-cell-functionality-for-adoptive-cell-therapy-of-malignant-melanoma
#17
Maarten A Ligtenberg, Yago Pico de Coaña, Taisia Shmushkovich, Yuya Yoshimoto, Iva Truxova, Yuan Yang, Monica Betancur-Boissel, Alexey V Eliseev, Alexey D Wolfson, Rolf Kiessling
Adoptive cell therapy (ACT) is becoming a prominent alternative therapeutic treatment for cancer patients relapsing on traditional therapies. In parallel, antibodies targeting immune checkpoint molecules, such as cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) and cell death protein 1 pathway (PD-1), are rapidly being approved for multiple cancer types, including as first line therapy for PD-L1-expressing non-small-cell lung cancer. The combination of ACT and checkpoint blockade could substantially boost the efficacy of ACT...
April 13, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29733743/use-of-an-animal-model-to-test-whether-non-alcoholic-fatty-liver-disease-increases-the-risk-of-idiosyncratic-drug-induced-liver-injury
#18
Alastair Mak, Tiffany Cho, Jack Uetrecht
Clinical evidence suggests that most idiosyncratic drug-induced liver injury (IDILI) is immune-mediated. The danger hypothesis suggests that liver injury and inflammation would increase the risk of an immune response leading to IDILI. Therefore, a reasonable hypothesis would be that an underlying chronic liver disease such as non-alcoholic steatohepatitis (NASH) would increase the risk of developing IDILI due to inflammation and release of danger signals from damaged cells. In order to test this hypothesis, mice were fed a methionine-/choline-deficient (MCD) diet that produces a consistent NASH phenotype, along with amodiaquine (AQ) - a drug known to cause IDILI in humans...
December 2018: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/29730461/evolution-of-checkpoint-inhibitors-for-the-treatment-of-metastatic-gastric-cancers-current-status-and-future-perspectives
#19
REVIEW
Julien Taieb, Markus Moehler, Narikazu Boku, Jaffer A Ajani, Eduardo Yañez Ruiz, Min-Hee Ryu, Silke Guenther, Vikram Chand, Yung-Jue Bang
BACKGROUND: Standard treatment options for patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC) are associated with limited efficacy and some toxicity. Recently, immunotherapy with antibodies that inhibit the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) interaction has emerged as a new treatment option. This manuscript reviews early-phase and late-phase trials of immunotherapy in advanced GC/GEJC. METHODS: Searches for studies of immunotherapy in GC/GEJC were performed using PubMed, ClinicalTrials...
April 22, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29729943/phenotype-penetrance-and-treatment-of-133-ctla-4-insufficient-individuals
#20
Charlotte Schwab, Annemarie Gabrysch, Peter Olbrich, Virginia Patiño, Klaus Warnatz, Daniel Wolff, Akihiro Hoshino, Masao Kobayashi, Kohsuke Imai, Masatoshi Takagi, Ingunn Dybedal, Jamanda A Haddock, David Sansom, Jose M Lucena, Maximilian Seidl, Annette Schmitt-Gräff, Veronika Reiser, Florian Emmerich, Natalie Frede, Alla Bulashevska, Ulrich Salzer, Desirée Schubert, Seiichi Hayakawa, Satoshi Okada, Maria Kanariou, Zeynep Yesim Kucuk, Hugo Chapdelaine, Lenka Petruzelkova, Zdenek Sumnik, Anna Sediva, Mary Slatter, Peter D Arkwright, Andrew Cant, Hanns-Martin Lorenz, Thomas Giese, Vassilios Lougaris, Alessandro Plebani, Christina Price, Kathleen E Sullivan, Michel Moutschen, Jiri Litzman, Tomas Freiberger, Frank L van de Veerdonk, Mike Recher, Michael H Albert, Fabian Hauck, Suranjith Seneviratne, Jana Pachlopnik Schmid, Antonios Kolios, Gary Unglik, Christian Klemann, Carsten Speckmann, Stephan Ehl, Alan Leichtner, Richard Blumberg, Andre Franke, Scott Snapper, Sebastian Zeissig, Charlotte Cunningham-Rundles, Lisa Giulino-Roth, Olivier Elemento, Gregor Dückers, Tim Niehues, Eva Fronkova, Veronika Kanderová, Craig D Platt, Janet Chou, Talal Chatila, Raif Geha, Elizabeth McDermott, Su Bunn, Monika Kurzai, Ansgar Schulz, Laia Alsina, Ferran Casals, Angela Deyà-Martinez, Sophie Hambleton, Hirokazu Kanegane, Kjetil Taskén, Olaf Neth, Bodo Grimbacher
BACKGROUND: Cytotoxic-T-lymphocyte-antigen-4 (CTLA-4) is a negative immune regulator. Heterozygous CTLA4 germline mutations can cause a complex immune dysregulation syndrome in humans. OBJECTIVE: To characterize the penetrance, the clinical features and the best treatment options in 133 CTLA4 mutation carriers. METHODS: Genetics, clinical features, laboratory values, and outcome of treatment options were assessed in a worldwide cohort of CTLA4 mutation carriers...
May 3, 2018: Journal of Allergy and Clinical Immunology
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