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Conventional Therapies Deplete Brain-Infiltrating Adaptive Immune Cells in a Mouse Model of Group 3 Medulloblastoma Implicating Myeloid Cells as Favorable Immunotherapy TargetsMedulloblastoma is the most common childhood brain cancer. Mainstay treatments of radiation and chemotherapy have not changed in decades and new treatment approaches are crucial for the improvement of clinical outcomes. To date, immunotherapies for medulloblastoma have been unsuccessful, and studies investigating the immune microenvironment of the disease and the impact of current therapies are limited.
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Targeting cross-presentation as a route to improve the efficiency of peptide-based cancer vaccinesCross-presenting dendritic cells (DC) offer an attractive target for vaccination due to their unique ability to process exogenous antigens for presentation on MHC class I molecules. Recent reports have established that these DC express unique surface receptors and play a critical role in the initiation of anti-tumor immunity, opening the way for the development of vaccination strategies specifically targeting these cells.
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Temporally restricted activation of IFNβ signaling determines response to immune checkpoint therapyThe biological determinants of the response to immune checkpoint blockade (ICB) in cancer remain incompletely understood. Little is known about dynamic biological events that underpin therapeutic efficacy due to the inability to frequently sample tumours in patients.
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Dendritic cells and influenza A virus infectionInfluenza A virus (IAV) is a dangerous virus equipped with the potential to evoke widespread pandemic disease.
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Optimal conditions required for influenza A infection-enhanced cross-priming of CD8+ T cells specific to cell-associated antigensOur group has recently shown that influenza A virus (IAV) infection of allogeneic cells lead to enhanced cross-priming of TCD8+ specific to cellular antigens.
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Stimulation of alpha-1 adrenoceptors may intensify cutaneous inflammation in complex regional pain syndromeAlpha-1 adrenoceptors are overexpressed in the epidermis of a subgroup of patients with complex regional pain syndrome. Activating α 1 -adrenoceptors in epidermal cells increases production of the proinflammatory cytokine interleukin-6, a mediator of inflammation.
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Deciphering the Immunological Phenomenon of Adaptive Natural Killer (NK) Cells and Cytomegalovirus (CMV)Natural killer (NK) cells play a significant and vital role in the first line of defense against infection through their ability to target cells without prior sensitization. They also contribute significantly to the activation and recruitment of both innate and adaptive immune cells through the production of a range of cytokines and chemokines. In the context of cytomegalovirus (CMV) infection, NK cells and CMV have co-evolved side by side to employ several mechanisms to evade one another.
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Tumour draining lymph node-generated CD8 T cells play a role in controlling lung metastases after a primary tumour is removed but not when adjuvant immunotherapy is usedSurgical resection of cancer remains the frontline therapy for millions of patients annually, but post-operative recurrence is common, with a relapse rate of around 45% for non-small cell lung cancer. The tumour draining lymph nodes (dLN) are resected at the time of surgery for staging purposes, and this cannot be a null event for patient survival and future response to immune checkpoint blockade treatment. This project investigates cancer surgery, lymphadenectomy, onset of metastatic disease, and response to immunotherapy in a novel model that closely reflects the clinical setting. In a murine metastatic lung cancer model, primary subcutaneous tumours were resected with associated dLNs remaining intact, completely resected or partially resected.
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Skin tumor immunity: Site does matter for antigen presentation by DCsTimely mobilization of tumor antigen-bearing dendritic cells (DCs) from the periphery to the lymph nodes is critical for effective antitumor T-cell immunity
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Spitz Melanoma of Childhood With A Novel Promoter Hijacking Anaplastic Lymphoma Kinase (C2orf42-ALK) RearrangementWe present the case of a prepubescent man of African descent who developed a spitzoid melanocytic proliferation showing evidence of a novel promoter hijacking ALK-C2orf42 rearrangement, with atypical histology, clinically apparent metastatic disease, and abnormal cytogenetic findings, representing a rare genuine case of "Spitz melanoma of childhood."