The Gynecologic Cancer Initiative is delighted to share that GCI Researcher, Dr. Julian J. Lum, and his team were recently awarded with the 2023 Terry Fox New Frontiers Program Project Grant to support their research on tumour-driven immunosuppression. Alongside Dr. Julian J. Lum (UVIC), this incredible team includes Dr. Shoukat Dedhar (BCCRI/UBC), Dr. Robert Rottapel (Princess Margaret Cancer Centre/Univ. of Toronto), Drs. Poul Sorensen (BCCRI/UBC) and Seth Parker (BCCHRI), and Drs. David Goodlett (Univ. of Victoria) & Kyle Duncan (Vancouver Island University).
Dr. Lum and his team are based at the Deeley Research Centre (DRC) in Victoria, BC. This marks the first time any group at the DRC has received the TFRI Program Project Grant. This project has been provided with $2.4 million in funding from the TFRI and Lotte & John Hecht Memorial Foundation to support their four-prong research project over the next four years.
The Spatial Metabolome Hubble Project to Decipher Tumour-Driven Immunosuppression (MetaboHUB)
The immune system is the body’s natural defense against pathogens and other things that may harm our body– including cancerous cells. However, there are times when cancer can suppress the body’s defenses, allowing tumours to proliferate and spread. To address this, the field of immunotherapy has been focusing on how we can hone the immune system and improve its ability to detect and destroy tumour cells.
Dr. Lum and his team note that tumours and immune cells are often competing for the same metabolites, or fuel source. Not only that, but tumour cells are consuming a majority of these metabolites and create by-products that result in a poor microenvironment that is not conducive to immune cell effectiveness. As a result, immunotherapy is quite limited in the range of cancers it can treat. Immunotherapy has most notably shown promising results in treating blood cancers, but there has been little success in other tumour types, such as ovarian cancer.
Thus, the team’s project aims to use state-of-the-art “metabolic telescopes” to visualize cancer metabolomes (a cell’s collection of metabolites). Using this technology driven by mass spectroscopy imaging, they strive to better understand how tumours and their microenvironment suppress the immune system. They also seek to investigate ways in which immunosuppression can be overcome. This work has the potential to improve the efficacy of immunotherapy in hard-to-treat tumours, such as ovarian cancer.
Investigating Immunometabolism in Different Tumour Types
Project 1, led by Dr. Shoukat Dedhar, will focus on understanding how the adaptation of pancreatic cancer cells to their hypoxic (low oxygen) environment can lead to the development of immunosuppressive properties. Pancreatic cancer cells in hypoxic environments are known to alter their metabolism in a way that produces substances that can fight or suppress the immune system. As a result, this hinders the effects of immunotherapy.
Project 2, led by Drs. Julian J. Lum and Robert Rottapel, focuses on immunosuppression in ovarian cancer. Their project will investigate the mechanism by which amino acid metabolism by tumour cells can reduce immune cell activity in response to ovarian cancer. Their initial findings indicate that the amino acid methionine can hinder T cell activity. Thus, Dr. Lum and Dr. Rottapel intend to use the “metabolic telescope” to study the spatial distribution of methionine, identify which T-cells are being disarmed, and how this disarming can be prevented.
“Ovarian cancer is a unique tumor when it comes to how metabolism alters its behaviour especially because this cancer has a poor response to immunotherapy. By illuminating how metabolism shapes how the immune system responds, we hope to use sophisticated genome-engineering to make T cells more powerful of attacking the tumor cells. We are also excited about opportunities to potentially make T cells stronger by changing the type of nutritional and dietary intake, while patients receive immunotherapies,” says Dr. Lum.
Project 3 is led by Drs. Poul Sorensen and Seth Parker. This project focuses on how tumour cells deal with metabolic stress in specific cancer types, and how this may hinder the effectiveness of immunotherapy. To achieve this, they will be using advanced mass spectroscopy to measure changes in tumours’ metabolic composition and how this may affect surrounding immune cells, especially in pancreatic and ewing sarcomas.
Last but not least, for the project core, Drs. David Goodlett and Kyle Duncan will provide the advanced imaging technology to create local metabolic profiles within tumours. This will enable the team to understand why certain cell immune cells are more or less active in specific regions of a tumour.
All together, the Spatial Metabolome Hubble Project to Decipher Tumour-Driven Immunosuppression (MetaboHUB) will be the first of its kind to use metabolic mapping to unravel the mechanisms of tumour-driven immunosuppression. The team’s investigations of the tumour microenvironment and its relation to immune cell activity may help shed light on ways in which the limitations of immunotherapy can be overcome– thus increasing the potential for immunotherapy to become an effective option for more cancer patients– including those affected by ovarian cancer.
TFRI Funding for Gynecologic Cancer Research and Innovation
With Dr. Lum’s award being the most recent, the Terry Fox Research Institute (TFRI) has officially funded three outstanding projects led by GCI researchers. We are very grateful to the TFRI for recognizing and supporting our team’s vision to enhance the quality of care for gynecologic cancer patients.
On September 17, 2023, the Terry Fox Foundation will be hosting their annual Terry Fox Run, a fundraiser dedicated to raising money for innovative cancer research. We invite you all to participate in this incredible event as a runner, donor, or volunteer to show your support for this wonderful cause that has been funding a number of GCI-led projects.
About the Terry Fox New Frontiers Program Project Grant
The Terry Fox Research Institute provides many funding opportunities to promising cancer research teams across the country. In particular, the Terry Fox New Frontiers Program Project Grant was designed to provide support to research teams exploring new frontiers in cancer research. This program recognizes research efforts that have the potential to transform the way we diagnose, treat, and/or understand cancers. Depending on whether it is a new or renewal application, research groups may receive over $2.4M in grants over 4 years (if a new application) or $6M over 6 years (if a renewal application).