A $3M grant from the Australian Cancer Research Foundation (ACRF) will establish a custom-built microscopy centre to image the ‘dark space’ of cancer-immune interactions, which will enable new advances in cancer research.
Based at Sydney's Garvan Institute of Medical Research, the ACRF Centre for Intravital Imaging of Niches for Cancer Immune Therapy (ACRF INCITe Centre) will house two Australian-designed microscopes. This will enable researchers to see immune cells and molecules at the cancer site move and interact in real time – below the surface of tumours and deep inside tissues.
The ACRF INCITe Centre will address a major challenge in the treatment of cancer: why some patients respond to immunotherapies, designed to arm the immune system against cancer, while others do not.
“Cancers hide from the immune system in highly complex and dynamic environments that can’t be visualised by conventional microscopes,” says Chief Investigator Professor Tri Phan from the Garvan Institute. “The custom-built microscopes in the ACRF INCITe Centre will overcome the current limitations and allow us to finally answer questions that we have not been able to address before. Our goal is to make a promising cancer therapy even more effective for patients.”
“Never in ACRF’s history has backing bold ideas for cancer research been more crucial. We are proud to announce funding of this world-leading Australian research centre today to enable new discoveries that will lead to better patient outcomes,” says ACRF’s CEO Kerry Strydom.
Bridging a gap in immunotherapy
Immunotherapy has greatly advanced cancer treatment over the past four decades and is highly effective for some cancer patients, including for half of those with advanced melanoma.
However, immunotherapy is effective in less than 30% of patients with advanced lymphoma, kidney, bladder and lung cancer, and for those affected by breast, prostate and pancreatic cancer, the treatment is rarely effective.
“For immunotherapy to be more effective, we need to bridge the gap in our understanding of how cancer cells interact with their local microenvironment to adapt to constantly changing conditions and how they evade immune destruction. These interactions are often short-lived and occur in sites that are inaccessible to visualisation by conventional microscopic techniques,” says Chief Investigator Associate Professor Marina Pajic, from the Garvan Institute.
Imaging beyond current limits
The ACRF INCITe Centre will enable researchers to see inside tumours at unprecedented temporal and spatial resolutions. “This is the first intravital imaging centre dedicated to studying cancer–immune cell interactions in vivo and at the molecular level. It will give us a comprehensive view of how the immune system can work to fight cancer,” says Chief Investigator Professor Paul Timpson, from the Garvan Institute.
Two custom microscopes housed at the INCITe Centre – the ‘EndoNICHEscope’ and ‘Molecular NICHEscope’ – will enable researchers to study living tumours inside mouse models, in real time.
The EndoNICHEscope will allow researchers to identify cancer and immune cells in previously inaccessible regions of tumours, using cutting-edge two-photon excitation imaging techniques, innovative adaptive optics technology and a minimally invasive microendoscope developed at the Australian National University by Chief Investigator Dr Steve Lee. The Molecular NICHEscope will image dynamic cancer-immune cell interactions and signalling events in unprecedented detail, in otherwise inaccessible organs such as the lung and pancreas, using a state-of-the-art FLIM detection unit and sophisticated image processing software.
The INCITe Centre, scheduled to launch next year, unites an interdisciplinary team of world-class experts in cancer biology, physics and engineering at the Garvan Institute, the Australian National University, University of Technology Sydney, QIMR Berghofer, Harry Perkins Institute of Medical Research, the Centre for Cancer Biology and Olivia Newton-John Cancer Research Institute.
Collaborators from 23 research labs from across Australia will access the technology via a virtual network to investigate fundamental cancer biology, the role of cells, molecules and genes that regulate cancer-immune interactions, and new therapeutic approaches to enhance immunity against cancer.
The researchers will address crucial questions, such as how immune cells can be activated in a breast cancer, how cancer-immune interactions can be manipulated to target cancer cells lying dormant in niches of bones, and how cancer cells use ‘immune cloaking’ to stay undetected.
“The vision of the Centre is to implement radical new imaging technologies to investigate and manipulate the cancer–immune cell interactions. Thanks to our extensive clinical connections, we plan to progress any new discoveries to clinical trials as quickly as possible,” says Professor Phan.
Dr Viviane Richter
Garvan Institute of Medical Research