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Modeling lymphoma evolution and clinical trajectory using multiomics

It’s their fifth cycle of funding for researchers at the BC Cancer Centre for Lymphoid Cancer who are part of the renewal of a coveted Terry Fox New Frontiers Program Projects Grant, following the 2022 competition. 

“It’s a privilege and honour to have this PPG award. The grant is quite unique in the landscape of Canadian funding and six million dollars over six years is the flagship of funding for large teams,” says the Centre’s research director Dr. Christian Steidl, who is now enjoying his second renewal as the team’s project leader. But it is not just the size of the PPG that has value for him. “The PPG keeps the team spirit alive because you are formally tied together and think collaboratively instead of wandering off in your own individual research direction.”

Past successes under PPG funding

With previous funding the lymphoma team defined the biological underpinnings of lymphoma through genomics and sequencing. “These studies have provided basic descriptions about what’s going on in the genetics of tumour cells and we have translated some of that information into tangible biomarker assays that are now a biological foundation of diagnosis in certain lymphoma types and have been translated into the World Health Organization classification system of lymphoid  neoplasms,” he explains. “We also identified molecular targets that have been investigated in clinical trials and are now fully developed drugs at the cusp of being used in standard of care for lymphoma patients.”

 

Into the future

With their new award, the BC Cancer team will use novel technologies in single-cell sequencing and histology imaging (e.g. imaging mass cytometry) to study how lymphoma cancer cells communicate with each other and their surrounding ecosystem of immune cells in their direct vicinity. “We can also develop novel therapies targeting this ecosystem and these therapies go hand in hand with the diagnostics we are also developing,” Steidl explains. In previous and ongoing investigations, the team developed sophisticated ways to look at genes and molecules with unprecedented precision and resolution. “These novel technologies in our current research allow for the description of changes in tumours, cell by cell, and also the visualization of the altered micro-architecture of lymph nodes and other organs involved with the lymphoma.”

An advantage of their study, he says, is the parallel investigation of multiple types of molecules in each cell and each patient with knowledge of the ultimate treatment outcome. “This gives us the opportunity to integrate layers of information into one comprehensive model with the goal to understand the diverse causes that lead to a specific lymphoma diagnosis and resistance to treatment.”

Steidl is optimistic about the progress being made. He says patients should remain hopeful. “We are on the right track. There are so many examples of how we have overcome challenges and surpassed expectations – but not for everyone. For the patients that have need of hope, they have a legitimate reason to believe in it because we are making progress as we speak.”