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https://www.readbyqxmd.com/read/28641100/bruton-s-tyrosine-kinase-btk-as-a-promising-target-in-solid-tumors
#1
REVIEW
J Molina-Cerrillo, T Alonso-Gordoa, P Gajate, E Grande
Bruton's tyrosine kinase (BTK) is a non-receptor intracellular kinase that belongs to the TEC-family tyrosine kinases together with bone marrow-expressed kinase (BMX), redundant-resting lymphocyte kinase (RLK), and IL-2 inducible T-Cell kinase (ITK). All these proteins play a key role in the intracellular signaling of both B and T lymphocytes. Recently, some preclinical data have demonstrated that BTK is present in certain tumor subtypes and in other relevant cells that are contributing to the tumor microenvironment such as dendritic cells, macrophages, myeloid derived suppressor cells and endothelial cells...
June 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28639391/an-investigation-of-the-relationship-between-recurrent-spontaneous-abortion-and-memory-t-follicular-helper-cells
#2
Xiaorui Luan, Xiaomin Kang, Weiping Li, Qian Dong
PROBLEM: Immune tolerance with respect to a semi-allogeneic fetus plays a key role in the establishment of a pregnancy. Memory T follicular helper (Tfh) cells have a central role in the regulation of the adaptive immune response. Much of our knowledge of memory Tfh cells' function comes from immune-related diseases. However, the true physiological characteristics of memory Tfh cells and their mode of action in pregnancy remain unclear. METHODS OF STUDY: Deciduas and blood were obtained from 25 recurrent spontaneous abortion (RSA) patients undergoing surgical abortion and 19 normal women in early pregnancy undergoing elective termination...
June 21, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28637884/vaccination-establishes-clonal-relatives-of-germinal-center-t-cells-in-the-blood-of-humans
#3
Antje Heit, Frank Schmitz, Sarah Gerdts, Britta Flach, Miranda S Moore, Jonathan A Perkins, Harlan S Robins, Alan Aderem, Paul Spearman, Georgia D Tomaras, Stephen C De Rosa, M Juliana McElrath
Germinal center T follicular helper cells (GCTfh) in lymphatic tissue are critical for B cell differentiation and protective antibody induction, but whether GCTfh establish clonal derivatives as circulating memory T cells is less understood. Here, we used markers expressed on GCTfh, CXCR5, PD1, and ICOS, to identify potential circulating CXCR5(+)CD4(+) Tfh-like cells (cTfh) in humans, and investigated their functional phenotypes, diversity, and ontogeny in paired donor blood and tonsils, and in blood after vaccination...
June 21, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28636875/effects-of-prenatal-binge-like-ethanol-exposure-and-maternal-stress-on-postnatal-morphological-development-of-hippocampal-neurons-in-rats
#4
Ewa Jakubowska-Dogru, Birsen Elibol, Ilknur Dursun, Sinan Yürüker
BACKGROUND: Alcohol is one of the most commonly used drugs of abuse negatively affecting human health and it is known as a potent teratogen responsible for fetal alcohol syndrome (FAS), which is characterized by cognitive deficits especially pronounced in juveniles but ameliorating in adults. Searching for the potential morphological correlates of these effects, in this study, we compared the course of developmental changes in the morphology of principal hippocampal neurons in fetal-alcohol (A group), intubated control (IC group), and intact control male rats (C group) over a protracted period of the first two postnatal months...
June 18, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28636292/-head-and-neck-cancer-promising-results-of-immunotherapy
#5
Aurélie Sivade, Djamila Bensaid, Yan Monnier, Keyvan Shabafrouz, Hanan Bouchaab, Valérie Cristina
Immunotherapy, especially checkpoint inhibitors such as anti-PD1 and anti-PDL1 antibodies, has changed the standard of care and the prognosis of melanoma, but also more recently of lung cancer, renal cancer and Hodgkin lymphoma. Results of preliminary studies in head and neck squamous cell carcinoma (HNSCC) as well as in less frequent tumors of the region, such as nasopharyngeal carcinoma and high grade salivary gland carcinoma, are also promising. Indeed, in a recent phase 3 study, the PD1 inhibitor nivolumab has recently demonstrated a significant improvement in overall survival for platin-resistant recurrent and/or metastatic HNSCC...
May 17, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28635639/immune-checkpoints-as-a-target-for-colorectal-cancer-treatment
#6
REVIEW
Alessandro Passardi, Matteo Canale, Martina Valgiusti, Paola Ulivi
Anti-tumor immunity is a new line of research for the treatment of patients with solid tumors. In this field, negative regulators of the immune system called immune checkpoints play a key role in limiting antitumor immunologic responses. For this reason, immune checkpoint-inhibiting agents, such as those directed against cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death-1 receptor (PD1) and its ligand PD-L1, have been developed as antitumor drugs, producing interesting results in preclinical and clinical studies...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28624961/phenotypic-and-functional-characterization-of-t-cells-in-white-matter-lesions-of-multiple-sclerosis-patients
#7
Gijsbert P van Nierop, Marvin M van Luijn, Samira S Michels, Marie-Jose Melief, Malou Janssen, Anton W Langerak, Werner J D Ouwendijk, Rogier Q Hintzen, Georges M G M Verjans
T cells are considered pivotal in the pathology of multiple sclerosis (MS), but their function and antigen specificity are unknown. To unravel the role of T cells in MS pathology, we performed a comprehensive analysis on T cells recovered from paired blood, cerebrospinal fluid (CSF), normal-appearing white matter (NAWM) and white matter lesions (WML) from 27 MS patients with advanced disease shortly after death. The differentiation status of T cells in these compartments was determined by ex vivo flow cytometry and immunohistochemistry...
June 17, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28616701/predictive-value-of-pd-l1-based-on-mrna-level-in-the-treatment-of-stage-iv-melanoma-with-ipilimumab
#8
C Brüggemann, M C Kirchberger, S M Goldinger, B Weide, A Konrad, M Erdmann, D Schadendorf, R S Croner, L Krähenbühl, K C Kähler, C Hafner, W Leisgang, F Kiesewetter, R Dummer, G Schuler, M Stürzl, L Heinzerling
INTRODUCTION: PD-L1 is established as a predictive marker for therapy of non-small cell lung cancer with pembrolizumab. Furthermore, PD-L1 positive melanoma has shown more favorable outcomes when treated with anti-PD1 antibodies and dacarbazine compared to PD-L1 negative melanoma. However, the role of PD-L1 expression with regard to response to checkpoint inhibition with anti-CTLA-4 is not clear, yet. In addition, the lack of standardization in the immunohistochemical assessment of PD-L1 makes the comparison of results difficult...
June 14, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28613923/the-era-of-checkpoint-blockade-in-lung-cancer-taking-the-brakes-off-the-immune-system
#9
Edmund K Moon, Corey J Langer, Steven M Albelda
Despite recent advances with targeted kinase inhibitors and better tolerated chemotherapy, the treatment of metastatic non-small cell lung cancer (NSCLC) remains suboptimal. One recent advance that holds great promise is immunotherapy - an approach that enhances a patient's immune system to better recognize and react to abnormal cells. The most successful immunotherapeutic strategy to date uses antibodies to block inhibitory receptors (also called "checkpoints") that are upregulated on the T cells that infiltrate the tumor...
June 14, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28611624/flare-up-of-rheumatoid-arthritis-by-anti-ctla-4-antibody-but-not-by-anti-pd1-therapy-in-a-patient-with-metastatic-melanoma
#10
Nicoletta F Jaberg-Bentele, Michael Kunz, Shatha Abuhammad, Reinhard Dummer
A 47-year-old female patient with rheumatoid arthritis (RA) treated with methotrexate, was diagnosed with metastatic melanoma. After surgical removal of the tumor, the patient started treatment with ipilimumab while methotrexate was stopped. One week after initiation of ipilimumab, the patient developed typical symptoms of RA. Analgetic therapy was started. After 4 cycles of ipilimumab, melanoma progression was radiologically evident. The treatment plan was changed to pembrolizumab (anti-PD1 antibody), and the patient did not show active signs of RA anymore...
January 2017: Case Reports in Dermatology
https://www.readbyqxmd.com/read/28610825/integrating-next-generation-dendritic-cell-vaccines-into-the-current-cancer-immunotherapy-landscape
#11
REVIEW
Abhishek D Garg, Pierre G Coulie, Benoit J Van den Eynde, Patrizia Agostinis
Cancer immunotherapy is experiencing a renaissance spearheaded by immune checkpoint inhibitors (ICIs). This has spurred interest in 'upgrading' existing immunotherapies that previously experienced only sporadic success, such as dendritic cells (DCs) vaccines. In this review, we discuss the major molecular, immunological, and clinical determinants of existing first- and second-generation DC vaccines. We also outline the future trends for next-generation DC vaccines and describe their major hallmarks and prerequisites necessary for high anticancer efficacy...
June 10, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28609681/epigenetic-modulation-in-cancer-immunotherapy
#12
REVIEW
Stuart J Gallagher, Elena Shklovskaya, Peter Hersey
The success of immune checkpoint inhibitors in cancer immunotherapy has been widely heralded. However many cancer patients do not respond to immune checkpoint therapy and some relapse due to acquired tumor resistance. Epigenetic targeting may be beneficial in cancer immunotherapy by reversing immune avoidance and escape mechanisms employed by cancer cells, as well as by modulating immune cell differentiation and function. In this manuscript we review recent findings suggesting how epigenetics may be used to improve cancer immunotherapy...
June 10, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28607114/varicella-zoster-virus-specific-cellular-immune-responses-to-the-live-attenuated-zoster-vaccine-in-young-and-older-adults
#13
Adriana Weinberg, Jennifer Canniff, Nadine Rouphael, Aneesh Mehta, Mark Mulligan, Jennifer A Whitaker, Myron J Levin
The incidence and severity of herpes zoster (HZ) increases with age. The live attenuated zoster vaccine generates immune responses similar to HZ. We compared the immune responses to zoster vaccine in young and older to adults to increase our understanding of the immune characteristics that may contribute to the increased susceptibility to HZ in older adults. Young (25-40 y; n = 25) and older (60-80 y; n = 33) adults had similar magnitude memory responses to varicella-zoster virus (VZV) ex vivo restimulation measured by responder cell-frequency and flow cytometry, but the responses were delayed in older compared with young adults...
June 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28605998/primary-cutaneous-cd4-small-medium-pleomorphic-t-cell-lymphoproliferative-disorder-a-case-series
#14
Martina Maurelli, Chiara Colato, Paolo Gisondi, Giampiero Girolomoni
BACKGROUND: Primary cutaneous CD4(+) small/medium T-cell lymphoproliferative disorder (CD4(+) PCSM-LPD) is defined by a predominance of small- to medium-sized CD4(+) pleomorphic T cells and a favorable clinical course. OBJECTIVE: We performed a retrospective analysis of 6 patients with CD4(+) PCSM-LPD and reviewed the literature to address questions about its diagnosis, treatment, and prognosis. METHODS: Patients were 3 men and 3 women with a median age of 50 years...
June 1, 2017: Journal of Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/28604555/immune-related-neurological-symptoms-in-an-adolescent-patient-receiving-the-checkpoint-inhibitor-nivolumab
#15
Dmitry Tchapyjnikov, Alexandra J Borst
Immune checkpoint inhibitors are a novel group of immunotherapeutic agents for the treatment of cancer. Immune-related adverse events, including neurological symptoms, have been associated with these agents. We present the case of an adolescent with refractory Hodgkin lymphoma treated with nivolumab, a PD1 inhibitor, who developed Hashimoto thyroiditis, posterior reversible encephalopathy syndrome causing seizures, as well as urinary retention, truncal/appendicular spasticity, dysphagia, and a progressive encephalopathy that was clinically consistent with a diagnosis of progressive encephalopathy with rigidity and myoclonus, a stiff-person-syndrome spectrum disorder...
June 9, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28601918/osimertinib-reactivated-immune-related-colitis-after-treatment-with-anti-pd1-antibody-for-non-small-cell-lung-cancer
#16
Tomoyoshi Takenaka, Koji Yamazaki, Naoko Miura, Naohiko Harada, Sadanori Takeo
We reported a case of relapsing immune-related colitis (initially caused by nivolumab) following osimertinib therapy for lung adenocarcinoma. A 45-year-old female who had never smoked was diagnosed with adenocarcinoma of the lung and underwent surgical resection. Four years after surgical resection, she was diagnosed with recurrent disease and was eventually treated with nivolumab as third-line therapy. One month after the completion of nivolumab therapy, the patient reported abdominal pain and frequent diarrhea...
June 10, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28600190/understanding-the-checkpoint-blockade-in-lung-cancer-immunotherapy
#17
REVIEW
Maria G Dal Bello, Angela Alama, Simona Coco, Irene Vanni, Francesco Grossi
Immunotherapies have changed the treatment strategy of some types of tumor including melanoma and, more recently, non-small-cell lung cancer (NSCLC). Immune checkpoints are crucial for the maintenance of self-tolerance and it is known that some tumors use checkpoint systems to evade antitumor immune response. The treatment of advanced NSCLC by immune-checkpoint blockade targeting the PD1/PDL1 and CTLA4 pathways has led to significant clinical benefit either as monotherapy or in combination therapy. Moreover, checkpoint receptors such as LAG3, TIM3 and KIRs are also being investigated as potential immunotherapeutic targets...
June 7, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28597150/erratum-to-sarcopenic-overweight-is-associated-with-early-acute-limiting-toxicity-of-anti-pd1-checkpoint-inhibitors-in-melanoma-patients
#18
Valentine Heidelberger, François Goldwasser, Nora Kramkimel, Anne Jouinot, Olivier Huillard, Pascaline Boudou-Rouquette, Johan Chanal, Jennifer Arrondeau, Nathalie Franck, Jérôme Alexandre, Benoît Blanchet, Karen Leroy, Marie-Françoise Avril, Nicolas Dupin, Sélim Aractingi
No abstract text is available yet for this article.
June 9, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28596157/-18-f-fdg-pet-and-ct-scan-detect-new-imaging-patterns-of-response-and-progression-in-patients-with-hodgkin-lymphoma-treated-by-anti-pd1-immune-checkpoint-inhibitor
#19
Laurent Dercle, Romain-David Seban, Julien Lazarovici, Lawrence Schwartz, Roch Houot, Samy Ammari, Alina Danu, Véronique Edeline, Aurélien Marabelle, Vincent Ribrag, Jean-Marie Michot
The response evaluation criteria in patients with Hodgkin Lymphoma (HL) were designed for the assessment of chemotherapy and targeted molecular agents. We investigated the accuracy of 3-month-(18)F-FDG-PET/CT for the identification of HL patients (pts) responding to immune-checkpoint blockade by Anti-Programmed Death 1 antibodies (anti-PD1). We also reported the frequency of new immune patterns of response and progression. Methods: Retrospectively, we recruited consecutive HL patients treated by anti-PD1 (Pembrolizumab or Nivolumab) at Gustave Roussy, Villejuif, France, from 2013-2015...
June 8, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28595520/a-case-of-fulminant-type-1-diabetes-following-anti-pd1-immunotherapy-in-a-genetically-susceptible-patient
#20
Manuel Araújo, Dário Ligeiro, Luís Costa, Filipa Marques, Helder Trindade, José Manuel Correia, Candida Fonseca
Programmed cell death-1 protein (PD-1) is an immune checkpoint that has gained popularity in the treatment of several advanced cancers. Inhibiting this checkpoint is known to enhance immune response, but is also known to diminish immune tolerance and to increase autoimmune toxicity. We discuss a case of rapid onset fulminant Type 1 diabetes induced by treatment with anti-programmed cell death-1 monoclonal antibody, nivolumab, in a patient with late-stage non-small-cell lung adenocarcinoma. The patient had no history of previous diabetes but did reveal a high-risk genotype for Type 1 diabetes development (DR3-DQ2; DR4-DQ8)...
June 2017: Immunotherapy
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