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Investigating The Dynamic Interactions Between Immune And Cancer Cells Using Two-photon Intravital Microscopy
Funder
National Health and Medical Research Council
Funding Amount
$401,361.00
Summary
Immune cells normally aid tumour destruction, but in some situations do the reverse and promote tumour spread. We will utilize cutting edge techniques including 2-photon microscopy together with novel transgenic mouse models to track immune cells in real time during tumour development in order to identify what factors determine a positive versus negative outcome. This will give us an unprecedented opportunity to ‘see’ how these cells interact with malignant cells which could lead to novel therap ....Immune cells normally aid tumour destruction, but in some situations do the reverse and promote tumour spread. We will utilize cutting edge techniques including 2-photon microscopy together with novel transgenic mouse models to track immune cells in real time during tumour development in order to identify what factors determine a positive versus negative outcome. This will give us an unprecedented opportunity to ‘see’ how these cells interact with malignant cells which could lead to novel therapeutic approaches.Read moreRead less
Cancer immunology has emerged as a fundamental discipline of oncology and overwhelming new data from large patient studies reveals the importance of the immune reaction in patient prognosis. Professor Smyth has established a large body of work indicating that the immune reaction is rate limiting for the development of tumours. His previous fundamental work forms a platform to launch new studies that will greatly increase the sophistication with which we understand the various immune mechanisms t ....Cancer immunology has emerged as a fundamental discipline of oncology and overwhelming new data from large patient studies reveals the importance of the immune reaction in patient prognosis. Professor Smyth has established a large body of work indicating that the immune reaction is rate limiting for the development of tumours. His previous fundamental work forms a platform to launch new studies that will greatly increase the sophistication with which we understand the various immune mechanisms that control tumour initiation, growth and metastases. It is a major goal of Professor Smyth’s Australia Fellowship to understand why some tumours may be controlled by the immune response while others are apparently not. He has established mouse models of cancer where these questions can be directly addressed for the first time.Read moreRead less
Generating Stronger And Smarter T Cells For Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$310,332.00
Summary
White blood cells from cancer patients can be modified in the laboratory to react against tumours. These cells can then be given back to the patient, which can sometimes cause cancer regression. However, often the white blood cells lack strength, or they lack the ability to distinguish between tumour and normal tissues of the body. In this project we seek to make stronger and smarter white blood cells that can deliver a lethal hit against tumours without damaging essential organs of the body.
Identification And Targeting Of A Potent NK Cell “checkpoint” In Tumour Immunity
Funder
National Health and Medical Research Council
Funding Amount
$470,144.00
Summary
Cancer must evade detection by the immune system in order to develop. Natural Killer (NK) cells can detect and kill cancer cells. We have discovered a potent "checkpoint" in the NK cell activation pathway that desensitizes NK cells to growth factors and switches off their activation and killer function. When this checkpoint is inhibited, NK cells become hyper-activated and prevent most types of cancer metastasis in mice. Targeting this checkpoint in humans could revolutionise cancer therapy
Exploiting The Cross Talk Between Tuft Cells And Group 2 Innate Lymphoid Cells For Tissue Homeostasis And Disease
Funder
National Health and Medical Research Council
Funding Amount
$831,162.00
Summary
The project investigates the cellular cross talk within the gastric mucosa between tuft cells, a rare epithelial cell type, and tissue-resident group 2 innate lymphoid cells (ILC2). The tuft cell/ILC2 axis is driven by the two cytokines interleukin (IL)-25 and IL-13 and is required for tissue homeostasis but turns pro-tumourigenic in the context of chronic inflammation. Our investigation will dissect the underlying mechanisms using a combination of mouse models, immunology and bioinformatics.
I am a practising hospital physician and a trained scientist and am widely acknowledged at the world leader in my field of study, asbestos cancers. Our latest research discoveries have put us on the threshold of bold new approaches to curing the scourge of these cancers and finding better blood tests but this work now requires extra attention from me to bring it to fruition. A Practitioner Fellowship is an ideal way for me to continue to lead this exciting research.
Adenosine Receptor Antagonists As Immunotherapeutic Agents For Cancer
Funder
National Health and Medical Research Council
Funding Amount
$555,779.00
Summary
We have shown that drugs that block immunosuppressive adenosine receptors can improve anti-tumour immune responses and consequently enhance the effectiveness of chemotherapy. These drugs are already known to be well-tolerated in humans and so have great potential for clinical development. We propose to determine the therapeutic response achieved with these drugs in combination with established cancer treatments involving radiotherapy and immune based therapies.
The Role Of The Actomyosin Cytoskeleton In T Cell-mediated Anti-tumour Immunity
Funder
National Health and Medical Research Council
Funding Amount
$616,950.00
Summary
T cells, specialised immune cells, are crucial in the defence against tumours. In order to reach cancerous target cells, T cells must enter tumour tissues from the blood stream and then effectively migrate in the extravascular space. This application aims to uncover the role of the cytoskeleton, a group of molecules driving cell shape change and motility, in the efficient execution of T cell anti-tumour function. These studies will aid the development of improved immunotherapies against cancer.