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Abacavir inhibits but does not cause self-reactivity to HLA-B*57:01-restricted EBV specific T cell receptorsPre-existing pathogen-specific memory T cell responses can contribute to multiple adverse outcomes including autoimmunity and drug hypersensitivity. How the specificity of the T cell receptor (TCR) is subverted or seconded in many of these diseases remains unclear. Here, we apply abacavir hypersensitivity (AHS) as a model to address this question because the disease is linked to memory T cell responses and the HLA risk allele, HLA-B*57:01, and the initiating insult, abacavir, are known.
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Making a Killer: Selecting the Optimal Natural Killer Cells for Improved ImmunotherapiesOver the past 20 years natural killer (NK) cell-based immunotherapies have emerged as a safe and effective treatment option for patients with relapsed or refractory leukemia. Unlike T cell-based therapies, NK cells harbor an innate capacity to eliminate malignant cells without prior sensitization and can be adoptively transferred between individuals without the need for extensive HLA matching.
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Anoctamins and Calcium Signalling: An Obstacle to EGFR Targeted Therapy in Glioblastoma?Glioblastoma is the most common form of high-grade glioma in adults and has a poor survival rate with very limited treatment options. There have been no significant advancements in glioblastoma treatment in over 30 years. Epidermal growth factor receptor is upregulated in most glioblastoma tumours and, therefore, has been a drug target in recent targeted therapy clinical trials.
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Improving compliance with swallowing exercise to decrease radiotherapy-related dysphagia in patients with head and neck cancerDysphagia, one of the most common complications in head and neck cancer (HNC) treated with radiotherapy, can severely affect patients’ quality of life. Currently, because no “gold standard” treatment exists, swallowing exercise remains the main rehabilitation strategy for dysphagia. However, patients’ compliance with long-term swallowing exercise is only 40%, thus, greatly compromising outcomes. This article aims to analyze thefactors influencing swallowing exercise compliance in patients with HNC and explains strategies developed to date for improved rehabilitation outcomes.
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Retinoic Acid Induces an IFN-Driven Inflammatory Tumour Microenvironment, Sensitizing to Immune Checkpoint TherapyWith immune checkpoint therapy (ICT) having reshaped the treatment of many cancers, the next frontier is to identify and develop novel combination therapies to improve efficacy. Previously, we and others identified beneficial immunological effects of the vitamin A derivative tretinoin on anti-tumour immunity.
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Comprehensive Testing of Chemotherapy and Immune Checkpoint Blockade in Preclinical Cancer Models Identifies Additive CombinationsAntibodies that target immune checkpoints such as cytotoxic T lymphocyte antigen 4 (CTLA‐4) and the programmed cell death protein 1/ligand 1 (PD-1/PD-L1) are now a treatment option for multiple cancer types. However, as a monotherapy, objective responses only occur in a minority of patients. Chemotherapy is widely used in combination with immune checkpoint blockade (ICB). Although a variety of isolated immunostimulatory effects have been reported for several classes of chemotherapeutics, it is unclear which chemotherapeutics provide the most benefit when combined with ICB.
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Cancer chemotherapy: insights into cellular and tumor microenvironmental mechanisms of actionChemotherapy has historically been the mainstay of cancer treatment, but our understanding of what drives a successful therapeutic response remains limited.
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CMV drives the expansion of highly functional memory T cells expressing NK-cell receptors in renal transplant recipientsCytomegalovirus (CMV) is a common opportunistic infection encountered in renal transplant recipients (RTRs) and may be reactivated without symptoms at any time post-transplant.
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PI3K activation in neural stem cells drives tumorigenesis which can be ameliorated by targeting the cAMP response element binding proteinA novel mouse model for glioma demonstrating that the PI3K pathway is important for initiation of tumorigenesis
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Most clinical anti-EGFR antibodies do not neutralize both wtEGFR and EGFRvIII activation in gliomaWe discovered a previously unknown major resistance mechanism in glioma in that most EGFR domain III-targeting antibodies do not neutralize EGFRvIII