Cancer Immunoregulation & Immunotherapy

The Cancer Immunoregulation and Immunotherapy Laboratory investigates how tumour-induced immunosuppression controls the three phases of cancer immunoediting. In particular, the laboratory has a strong interest in investigating the immunosuppressive role of regulatory T cells (Tregs), T cell anergy/exhaustion, the cytokine IL-23 and its associated cytokine family and immunosuppressive metabolites (adenosine) in the local tumour microenvironment using experimental and de novo mouse models of cancer.

In 2016, our group provided the first demonstration in pre-clinical tumor models that neoadjuvant compared to adjuvant immunotherapies were more effective in the eradicating of metastases in the context of cancer surgery. Our study has now spurred many of our colleagues to undertake new clinical trials in many cancer types to compare the efficacy of neoadjuvant to adjuvant immunotherapies. Excitingly, initial clinical trial studies reported promising data suggesting neoadjuvant compared to adjuvant immunotherapies further improved clinical outcomes. Ongoing work in the laboratory now aims to understand the key mechanism and pathways that are activated and/or required by neoadjuvant immunotherapy which may allow for selective targeting and further improvements of immunotherapies in general.

Clinicians are currently faced with the dilemma of what combination immunotherapies to test in different cancers. The laboratory has also developed a preclinical mouse model that allows the therapeutic index (antitumour efficacy vs immune-related adverse events (irAEs)) of antibodies targeting various immunomodulatory receptors to be simultaneously assessed for the first time. This model may be used to preclinically assess the therapeutic window of novel immunotherapy combinations in different tumour types. This will aid clinicians and pharmaceutical companies weigh up their risk/cost–benefit profile.

CURRENT RESEARCH

  • dissecting the immunological mechanisms underpinning the efficacy of neoadjuvant immunotherapy and cancer surgery
  • assessing combinations therapies targeted at the adenosinergic molecules in cancer and their mechanism of action
  • investigating the role of MAIT cells in cancer
  • assessing the role of the IL-23/IL-23R cytokine pathway in cancers particularly sarcomas

Staff

  • Dr Celia Jacoberger-Foissac, Research Officer
  • Dr Joshua Tay, Research Officer
  • Dr Elizabeth McDonald,Research Officer
  • Sergio Irac, Research Assistant
  • Hannah Triscott, PhD Student
  • Bryan Lye, PhD Student
  • Dr Harry Gasper, MPhil Student
  • Dr Liam Town, Laboratory Manager
  • Brodie Quine, Scientific Technical Officer
  • Andreea Zaharia, Scientific Technical Officer

Internal Collaborators

External Collaborators

  • Dr Mario Mandala, Papa Giovanni XXIII Hospital
  • Professor Christian Blank, Department of Medical Oncology, The Netherlands Cancer Institute
  • Professor Paolo Ascierto, National Cancer Institute (IRCCS) ‘G. Pascale Foundation’
  • Professor David Thomas, Kinghorn Cancer Centre
  • Dr Joe Yeung, Singapore General Hospital
  • Associate Professor Brett Hughes, Royal Brisbane & Women’s Hospital
  • Dr Charles Lin, Royal Brisbane & Women’s Hospital
  • Dr Ryan Sommerville, Royal Brisbane & Women’s Hospital
  • Associate Professor Martin Batstone, Royal Brisbane & Women’s Hospital
  • Dr Wayne Nicholls, Queensland Children’s Hospital
  • Professor David Fairlie,  Institute for Molecular Bioscience, University of Queensland
  • Dr Alexandra Corbett, Peter Doherty Institute, University of Melbourne

We gratefully acknowledge the support of the following funding agencies:

  • National Health and Medical Research Council (NHMRC)
  • Cancer Council of Queensland
  • Melanoma Research Alliance
  • Cancer Research Institute
  • Harry J. Lloyd Charitable Trust

Philanthropic Funding:

  • Summit to Sarcoma
  • Hare Family Philanthropy – Children’s Cancer Program
  • AP Eagers Foundation