Reshaping the immunosuppressive tumour microenvironment of brain cancer

2021 Honours opportunity

Supervisors: Prof Matthias Ernst and Dr Ashleigh Poh

Laboratory: Cancer and Inflammation

Subjects prerequisites: MED3LAB, MED3PRJ and/or GEN3LAB

Glioblastoma (GBM) is the most common and fatal type of primary malignant brain cancer. A hallmark of GBM is an immunologically “cold” tumour microenvironment characterised by an abundance of immunosuppressive myeloid cells, which limit anti-tumour immune responses. Thus, readily translatable strategies that can reprogram the immunosuppressive tumour microenvironment and promote the recruitment and activation of cytotoxic immune cells represent a major advancement for the treatment of GBM.

Elevated expression of the myeloid-specific kinase Haematopoietic Cell Kinase (HCK) is observed in most solid cancers and correlates with poor patient survival. We have previously shown that constitutive HCK activation promotes tumour growth and progression by facilitating the polarisation of myeloid cells towards an immunosuppressive endotype (Poh et. A; Cancer Cell 2017, Cancer Immunology Research 2020). Accordingly, genetic ablation or pharmacologic inhibition of HCK impairs colon and gastric tumour growth by reducing the abundance of immunosuppressive myeloid cells.

Given the role of HCK signaling in myeloid-driven immunosuppression, and the contribution of these cells in GBM, we hypothesise that targeting HCK will present new opportunities for the treatment of brain cancer.

The overall aims of this project are to:

  • Dissect the immunological mechanisms by which constitutive HCK activation or loss of HCK signaling influences GBM development and progression
  • Validate the therapeutic efficacy of novel HCK-specific small molecule inhibitors in preclinical models of GBM.

Students will work in state-of-the-art research laboratories of the School of Cancer Medicine /Olivia Newton-John Cancer Research Institute, which is embedded in the ONJ Cancer Centre. Students will gain experience in multidisciplinary techniques in tumour biology, immunology, molecular biology, and pre-clinical mouse models.

 

How do I apply?
Please complete and return your Ranked Entry Project Selection Form (available in the 2021 projects bookletby 5pm Friday 6 November 2020 to I.Poon@latrobe.edu.au

How do I find out more?
Discover more about La Trobe University’s School of Molecular Sciences/LIMS Honours opportunities
Contact the LTU Honours Coordinator, Dr Ivan Poon
Phone: 03 9479 6488
E-mail: I.Poon@latrobe.edu.au