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Research

Protocol for delivery of intraoperative immunotherapy to mice by surgical debulking of subcutaneous tumors

Pre-clinical studies developing novel therapies to prevent cancer recurrence require appropriate surgical models. Here, we present a protocol for surgical debulking of subcutaneous tumors in mice, which allows for intraoperative application of immunotherapy-loaded biomaterials. 

Research

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 used

Surgical 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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Spitz Melanoma of Childhood With A Novel Promoter Hijacking Anaplastic Lymphoma Kinase (C2orf42-ALK) Rearrangement

We 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."

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Platelets after burn injury–hemostasis and beyond

Burn injuries are common and often life-threatening trauma. With this trauma comes an interruption of normal hemostasis, with distinct impacts on platelets.

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Anti-metabolite chemotherapy increases LAG-3 expressing tumor-infiltrating lymphocytes which can be targeted by combination immune checkpoint blockade

Antibodies that target immune checkpoints such as cytotoxic T lymphocyte antigen 4, programmed cell death protein/ligand 1 are approved for treatment of multiple cancer types. 

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Invasive fungal disease in children with solid tumors: An Australian multicenter 10-year review

Invasive fungal disease (IFD) occurs less frequently during treatment for solid compared to hematological malignancies in children, and risk groups are poorly defined. Retrospective national multicenter cohort data (2004-2013) were analyzed to document prevalence, clinical characteristics, and microbiology of IFD.

Research

Dietary Vitamin D Increases Percentages and Function of Regulatory T Cells in the Skin-Draining Lymph Nodes and Suppresses Dermal Inflammation

Dietary vitamin D3 increased the suppressive activity of regulatory T cells in the skin-draining lymph nodes, which are poised to suppress dermal inflammation

Research

Rewiring endogenous genes in CAR T cells for tumour-restricted payload delivery

The efficacy of chimeric antigen receptor (CAR) T cell therapy in solid tumours is limited by immunosuppression and antigen heterogeneity. To overcome these barriers, 'armoured' CAR T cells, which secrete proinflammatory cytokines, have been developed. However, their clinical application has been limited because of toxicity related to peripheral expression of the armouring transgene. 

Research

Non-severe burn injury increases cancer incidence in mice and has long-term impacts on the activation and function of T cells

Recent evidence suggests that burn patients are at increased risk of hospital admission for infection, mental health conditions, cardiovascular disease and cancer for many years after discharge for the burn injury itself.

Research

Exploiting temporal aspects of cancer immunotherapy

Many mechanisms underlying an effective immunotherapy-induced antitumour response are transient and critically time dependent. This is equally true for several immunological events in the tumour microenvironment induced by other cancer treatments. Immune checkpoint therapy (ICT) has proven to be very effective in the treatment of some cancers, but unfortunately, with many cancer types, most patients do not experience a benefit.