Our People

Mark Smyth

Professor | Senior Scientist | Coordinator of Immunology Department

Immunology in Cancer & Infection

+61 7 3362 0222

mark.smyth@qimrberghofer.edu.au

 

CAREER HISTORY

Professor Mark Smyth is a Senior Scientist and Immunology Department Coordinator at QIMR Berghofer. He completed his PhD in 1988 and trained at the NCI (1988-1992), before commencing his independent research career in Australia. Over the last 20 years, he rekindled world-wide interest in cancer immune surveillance, defined immune-mediated dormancy of cancer, and the role of the host in chemotherapy and targeted therapy responses in mice and humans. More recently, he has provided new means of classifying natural killer cell (NK) subtypes and two new targets for cancer immunotherapy. He is a past winner of the Coley Medal and Brupbacher Foundation Prizes in Cancer Research. He is FAA, FAHMS and the highest cited immunologist in Australia. He is an Editor and Advisory Board Member for Cancer Discovery and Science, respectively.

 

CURRENT APPOINTMENTS

  • Coordinator, Department of Immunology, QIMR Berghofer
  • Head, Immunology in Cancer and Infection, QIMR Berghofer
  • Senior Scientist, NHMRC Investigator L3-T4
  • Honorary Professor, Queensland University of Technology
  • Honorary Professor, The University of Queensland

 

PREVIOUS APPOINTMENTS

2015-2019

  • NHMRC Senior Principal Research Fellow, QIMR Berghofer

2013–2014

  • NHMRC Australia Fellow, QIMR Berghofer

2007–2013

  • Honorary Professor, University of Melbourne
  • Honorary Professor, Monash University

2000–2013

  • Program Head, Cancer Immunology Program, Peter MacCallum Cancer Centre

2010–2013

  • NHMRC Australia Fellow, Peter MacCallum Cancer Centre

2007–2010

  • NHMRC Senior Principal Research Fellow, Peter MacCallum Cancer Centre

2000–2006

  • NHMRC Principal Research Fellow, Peter MacCallum Cancer Centre

1999–2000:

  • NHMRC Principal Research Fellow, Austin Research Institute

1998–2000

  • Associate Professor, Victoria University of Technology
  • Senior Fellow, Department of Medicine, Austin and Heidelberg Repatriation Medical Centre

1996–1998

  • Senior Associate, Department of Pathology, University of Melbourne

1994–1998

  • Wellcome Trust Senior Research Fellow in Medical Science, Austin Research Institute, Melbourne

1993

  • Senior Associate, Department of Surgery, Austin and Heidelberg Repatriation Hospitals, University of Melbourne
  • Douglas Wright Research Fellow of the NHMRC, Austin Research Institute, Melbourne

1991–1993

  • J. Martin Fellow of the NHMRC, Austin Research Institute, Melbourne

1989–1991

  • J. Martin Fellow of the NHMRC, Frederick Cancer Research and Development Center, NCI, USA

1988–1989

  • Visiting Fellow, Fogarty Visiting Program, Frederick Cancer Research and Development Center, NCI, USA

1988

  • Research Fellow, Grade I, Research Centre for Cancer and Transplantation, University of Melbourne

 

ORCID NUMBER

0000-0001-7098-7240

 

RESEARCHER ID

H-8709-2014

 

CURRENT AREAS OF RESEARCH

The Immunology in Cancer and Infection Laboratory focuses on advancing our understanding of the basic principles underlying an immune response to cancer (and metastases) and infection. We aim to further understand these processes at the molecular level, with particular emphasis on two major pathways of resistance to immunotherapy – namely: the CD226/CD96/TIGIT-CD155 receptor-ligand complex and the extracellular ATP/adenosine pathways. We also study the role of the innate immune system, in particular, the NK cell-ILC1/myeloid cross talk.

The Lab team has developed approaches to block these two pathways of immunotherapy resistance, including creating new agents to block lymphocyte CD96/TIGIT immune checkpoints or promote ATP accumulation while limiting adenosine-mediated immune suppression. Their findings are being used to develop more effective biological and cellular therapies for human cancer, in particular, melanoma, lung cancer, head and neck cancer, and haematological cancers, such as multiple myeloma, where we aim to treat minimal residual disease.

They are also deleting various genes in NK cells and myeloid cells in the context of tumour initiation and metastases, with a view to understanding the major mechanisms of immune suppression limiting NK cells and myeloid cell anti-tumour function.

 

RESEARCH HIGHLIGHTS

  • first characterised the specificity and transcriptional regulation of perforin and lymphocyte effector function
  • first defined a role for NK and NKT cells in tumour immune surveillance
  • proved that lymphocyte cytotoxicity was important in cancer immune surveillance
  • first defined a physiological role for TRAIL as a tumour suppressor
  • made key discoveries linking NK cells and adaptive T cell control of tumours and viruses
  • defined a role for NKG2D in cytokine and host protection from tumour initiation
  • demonstrated a unique combination of pathways that can potently reject established cancers in mice
  • first defined immune-mediated dormancy of cancer
  • defined the role of host inflammasome in chemotherapy responses
  • first defined CD73 and CD96 as new targets for cancer immunotherapy
  • defined CD96 as a novel immune checkpoint (Nature Immunology 2014)
  • demonstrated the anti-tumor effectiveness of targeting CD73 and adenosine A2A receptor (Cancer Cell 2016)
  • demonstrated neoadjuvant immunotherapy is superior to adjuvant immunotherapy in the context of surgery (Cancer Discovery, 2016)
  • demonstrated anti-metastatic activity of anti-CD96 antibodies alone and in combination with immune checkpoint blockade (Cancer Discovery 2016)
  • defined the TGF-b-mediated plasticity of NK cells in tumours (Nature Immunology 2017)
  • defined bone marrow IL-18 as critical in the prognosis and progression of multiple myeloma (Cancer Cell 2018)
  • defined the mechanism of action of anti-CD39 antibodies (Cancer Discovery 2019)
  • defined the role of NKG7 in NK cell anti-tumour function (Nature Immunology 2020)
  • defined the importance of CD226 in response to immunotherapy and a new mechanism of tumour-induced loss of CD8+T cell CD226 (Immunity, 2020)

 

PROFESSIONAL MEMBERSHIPS

2020–current: Editor at Cancer Discovery

2018-current: Compass Therapeutics Scientific Advisory Board, USA

2017–current: Tizona Therapeutics Scientific Advisory Board, USA

2017-current: Fellow of the Australian Academy of Science

2017-current: Senior Editor at Cancer Immunology Research

2016–current: Editorial Advisor at Science

2015-current: Fellow of the Australian Academy of Health and Medical Sciences

2012–current: Scientific Advisory Board of the Cancer Research Institute, USA

1995–current: Member of The American Association of Immunologists

1992–current: Member, Australasian Society for Immunology

 

AWARDS RECOGNITION

2020

  • NHMRC Investigator L3-T4

2019

  • High-end Foreign Expert in China. G20190001629

2017

  • Elected as a Fellow of the Australian Academy of Science

2015

  • Ashley Dunn Oration, Lorne Cancer Conference
  • Fellow of Australian Academy of Health and Medical Sciences
  • NHMRC Senior Principal Research Fellowship
  • Ranked 1st NHMRC Research Fellowships 2014 round
  • Ranked 1st NHMRC Development Grants 2014 round
  • Thomson Reuters Highly Cited Researchers – Immunology
  • QIMR Berghofer Ralph Doherty Prize

2012

  • Career Award, European Academy of Tumor Immunology

2011

  • Member of Academy of Cancer Immunology, Cancer Research Institute, USA
  • Elected to European Academy of Tumor Immunology

2010

  • NHMRC Australia Fellowship

2009

  • Glaxo Smith Kline Award for Excellence
  • ASI Gordon Ada Award

2007

  • Charles Rodolphe Brupbacher Foundation Prize
  • Gordon Ada Oration, ASI, Sydney

2007–2011

  • NHMRC Senior Principal Research Fellowship promotion

2004–2008

  • NHMRC Principal Research Fellowship renewal

2003

  • Commonwealth Health Minister’s Award for Excellence in Health and Medical Research – Finalist

2002

  • Cancer Research Institute, William B. Coley Award for Distinguished Research in Basic and Tumour Immunology

1999–2003

  • NHMRC Principal Research Fellowship

1998

  • AMGEN Medical Research Award

1995

  • Australian Academy of Science Gottschalk Medal

1994–1998

  • Wellcome Trust Senior Research Fellowship in Medical Science

1993

  • NH&MRC R. Douglas Wright Research Fellowship
  • Australian Life Sciences Research Award

1992

  • Sandoz Young Investigators Award (TSANZ – Canberra)

1991

  • NCI -FCRDC Certificate of Appreciation for Outstanding Performance

1989–1992

  • NH&MRC C. J. Martin Fellowship

1988–1989

  • NIH Fogarty Visiting Fellowship

 

EDUCATIONAL BACKGROUND

1985–1988: PhD, Research Centre for Cancer and Transplantation, Department of Pathology, University of Melbourne

1984: B.Sc. (Hons.) University of Melbourne (Pathology)

1981–1983: B.Sc. University of Melbourne (Biochemistry/Pathology)