Although the immune system has the ability to reject tumours, this sometimes does not occur, leading to cancer. There are many different types of cells that make up the immune system, including some which respond very early, called natural killer (NK) and NKT cells. These cells are the first line of defence against some tumours, although we do not understand how they recognise and respond to tumour cells. The aim of this project is to investigate the functional importance of both NK and NKT cell ....Although the immune system has the ability to reject tumours, this sometimes does not occur, leading to cancer. There are many different types of cells that make up the immune system, including some which respond very early, called natural killer (NK) and NKT cells. These cells are the first line of defence against some tumours, although we do not understand how they recognise and respond to tumour cells. The aim of this project is to investigate the functional importance of both NK and NKT cells in response to a range of different tumour types, including melanoma (skin cancer), lung carcinoma, breast carcinoma and sarcoma (connective tissue tumour). We will test the importance of each of these subsets by injecting these tumours into mice that have specific deficiencies in NK and-or NKT cells. If the NK or NKT cells are important, the tumours should grow more effectively when these immune cells are absent. We will also be able to put NK and-or NKT cells back into the mice to show directly that they are responsible for tumour rejection. Using a modification of this cell transfer approach, we will be able to inhibit special molecules that are normally produced by these cells that help them interact with other cells, and also help them attack the tumour cells. Collectively, the approaches outlined in this application allow us to determine which types of cells are important in response to a broad range of different tumour types, and also should tell us how these cells are able to attack the tumours. This information will be invaluable for the development of new strategies to use the patients immune system to attack cancer (known as immuno-therapy).Read moreRead less
The Role Of CD4+ T Cells In The Tumour Killing By CD8+ Memory T Cells.
Funder
National Health and Medical Research Council
Funding Amount
$303,000.00
Summary
It has been observed that human cancers grow in spite of the presence of tumour antigen specific memory CD8+ tumour killer T cells in the body. These memory killer cells are unable to kill the cancer. Our research work in a mouse model indicates that the CD8+ T cells can be activated to kill cancers if cancer antigen specific CD4+ T helper cells are activated. The mechanism how this happens is not clear. The role of regulatory or suppressor CD4+ T cells are also not known. In this proposal we wi ....It has been observed that human cancers grow in spite of the presence of tumour antigen specific memory CD8+ tumour killer T cells in the body. These memory killer cells are unable to kill the cancer. Our research work in a mouse model indicates that the CD8+ T cells can be activated to kill cancers if cancer antigen specific CD4+ T helper cells are activated. The mechanism how this happens is not clear. The role of regulatory or suppressor CD4+ T cells are also not known. In this proposal we wish to study the mechanism of how CD8+ memory T cells get activated to cancer killer cells by the CD4+ T helper cells. This information will help us to design better immunotherapies for cancer patients.Read moreRead less
WHAT IS THE RELATIVE ROLE OF TNF-RELATED APOPTOSIS-INDUCING LIGAND (TRAIL) IN TUMOR IMMUNITY?
Funder
National Health and Medical Research Council
Funding Amount
$85,660.00
Summary
Programmed cell death is a physiological process integral to the development and functioning of the immune system. A better understanding of the cellular effector cells and molecules that mediate cell death will provide valuable insight into designing better immunotherapeutic treatments of cancer. Members of the tumor necrosis factor (TNF) family of hormones and receptors are critically involved in the process of cell death. Within this family, several members have been well characterised and th ....Programmed cell death is a physiological process integral to the development and functioning of the immune system. A better understanding of the cellular effector cells and molecules that mediate cell death will provide valuable insight into designing better immunotherapeutic treatments of cancer. Members of the tumor necrosis factor (TNF) family of hormones and receptors are critically involved in the process of cell death. Within this family, several members have been well characterised and their functions ascribed. Some play an important role in the maintenance of immune cells , others in the movement of immune cells and organisation of lymphoid tissues. This proposal seeks to define the function of the recently discovered TNF-related apoptosis-inducing ligand (TRAIL). TRAIL mediates cell death of cancerous cells in culture but does not kill most normal tissues. This specificity for diseased tissue makes TRAIL a very promising candidate as an anti-tumor therapeutic. Until recently, very little was known regarding the natural physiological role of TRAIL. We have recently described the expression of TRAIL on liver natural killer cells and the anti-tumor activity of TRAIL against primary tumors and metastases. Importantly, TRAIL function appears to be regulated by an inflammatory mediator called interferon. We now wish to explore the role of TRAIL in tumor immunotherapies and tumor surveillance that requires interferon.Read moreRead less
Mechanisms Of T Cell Migration And Interactions In Tumours
Funder
National Health and Medical Research Council
Funding Amount
$609,385.00
Summary
Cancer is still a leading cause of death. Thus, there is great need to develop improved anti-cancer therapies, which could be achieved by boosting the body's own resources, i.e. the immune system. Using a functional imaging approach, i.e. two-photon microscopy, we will directly visualise how tumour cells are attacked by the immune system. Mechanistic insight into this process will serve as a basis for the development of improved immuno-therapeutic strategies that aim to target cancer cells.