PhD Scholarship - Manipulating the tumour microenvironment to enable cancer therapy
Supervisors: Associate Professor Michael Kershaw, Dr Clare Slaney, Associate Professor Phil Darcy.
We have developed combination immunotherapies that can eradicate the majority of large subcutaneous tumours of a variety of types including cancers of the kidney, colon and breast in mice. However, we have found that these same tumours respond poorly to therapy when implanted in orthotopic sites. We have determined that, for the renal tumour model, the tumour microenvironment of orthotopic tumours is significantly different from that of subcutaneous tumours. In particular, orthotopic tumours are relatively rich in cells and molecules associated with Th2 and M2 macrophage axes. The mechanistic contribution of these axes to the differential responses to therapy of renal and subcutaneous tumours is supported by our data showing that therapeutic responses of orthotopic disease is enhanced in mice deficient in the Th2 cytokine IL-13 or when the M2-associated chemokine CCL2 is neutralized. These findings suggest that the tissue of tumour implantation plays a major role in sculpting the tumour microenvironment. Furthermore, we have found that the presence of orthotopic tumours can reduce the efficacy of therapy on subcutaneous tumours, suggesting crosstalk exists between tumours to affect immune responses elicited by immunotherapy.
We wish to gain further insight into the differential tumour microenvironments of tumours in different anatomical sites, and in particular determine the tissue-specific contributors that sculpt the microenvironment. We will also determine the mechanism of crosstalk between concurrent tumours. Using material obtained from a rapid autopsy initiative, we will extend our studies into humans to determine cellular and molecular differences between microenvironments of tumours from various metastatic sites.
Information derived from these studies performed in physiologically relevant mouse tumour models, and in human metastatic disease, may lead to the design of immunotherapies that can be effective against tumours.This project is a collaboration between the Immune Innovation and Immunotherapy laboratories at the Peter MacCallum Cancer Centre.
- In the Immune Innovation (Kershaw, Slaney) laboratory, researchers are investigating novels ways to treat cancer, looking at the tumour microenvironment (the area immediately surrounding cancer tissue), genetic modification of immunity and testing new ideas in early phase proof-of-principle studies to determine their potential as cancer therapeutics.
- In the Immunotherapy (Darcy) laboratory, researchers focus on pre-clinical development of novel immune therapies for cancer, aiming to translate the most effective treatments into the clinic.
Area of study: Cancer
Approximate value: $26,288 per annum and is indexed at the Melbourne Research Scholarship rate
Tenure: 3.5 Years
Citizenship: Australian Citizen, Australian Permanent Resident, New Zealand Citizen, International (includes permanent residents of NZ)
Prior qualifications: Any. Preference will be given to applicants with prior qualifications in the health sciences field.
Student type: Graduate research
Enrolment status: Commencing students
Who can apply?
- Applicants must meet the entry requirements for PhD in the Faculty of Medical, Dental and Health Sciences, University of Melbourne.
- Preference will be given to applicants with prior qualifications in the health sciences field.
- The successful awardee must enrol and commence studies before 1st June 2016.
Interested applicants are invited to contact Michael Kershaw with a CV and submit an expression of interest.
Expressions of interest and enquiries should be made to: firstname.lastname@example.org by 4 April 2016.
The successful EOI applicant will be invited to complete a University of Melbourne online application for PhD course and scholarship.
Assessment can take up to six weeks and the formal assessment is subject to the entry requirements as listed in the University Handbook, including English language requirements.