Patients with high grade serous carcinoma (HGSC), a type of ovarian cancer, have limited treatment options. Current treatments, including chemotherapy and PARP inhibitors are unable to completely control the disease, which often metastasizes and recurs. Immunotherapy, which harnesses the body’s natural defense against cancer, has shown success in other cancers, but so far, it hasn’t been successful for patients with HGSC.
To overcome this, a team of Halifax-based researchers led by Dr. Jeanette Boudreau, a former Terry Fox New Investigator and now co-principal investigator of a new Terry Fox New Frontiers Program Project Grant (PPG), is expanding the focus from one type of immune cell to investigate how different immune cells, particularly those expressing a tool called CD16a, interact with each other to change outcomes for patients with HGSC.
The Boudreau laboratory has analyzed tumour samples from almost 1,000 patients using advanced digital pathology and computational biology techniques, identifying six distinct patterns of immune cell arrangement called “cellular neighbourhoods.”
In a study published earlier this year, the TFRI-funded team found that almost all patients had a mix of these neighbourhoods, but there were variations in the proportion of natural killer (NK) cells, T cells, macrophages and tumour cells. The study also revealed that patients with more CD16a positive immune cells had better survival outcomes. Those whose tumours were filled with neighbourhoods containing macrophages, T cells and NK cells with CD16a had better overall and progression-free survival.
“These patterns of immune neighbourhoods could be the key to developing more effective treatments in the future,” says Dr. Sarah Nersesian, the study’s first author and recent PhD graduate from Dalhousie University, where much of this work formed the foundation of her doctoral research under the mentorship of Dr. Boudreau.
“We think that CD16a+ cells are an important part of the puzzle. Our results show that the immune system is mobilized in response to HGSC in patients that are surviving well. The next job will be to sort out how this is regulated and controlled, and we hope to leverage this knowledge to maximize the immune response – and therefore treatment – for patients with HGSC,” says Dr. Boudreau.
Dr. Boudreau will continue working to develop immunotherapy approaches for ovarian cancer as a co-principal investigator of the new PPG which is led by Dr. Brad Nelson, a distinguished scientist, BC Cancer Research Institute, and director, Deeley Research Centre in Victoria.
"This PPG represents the next stage of research in our program and in the development of immunotherapies for ovarian cancer,” says Dr. Boudreau. “It also highlights the collaboration and continuity made possible through Terry Fox funding, which plays a key role in training the next generation of scientists.”
Similarly, Dr. Nersesian is advancing her research career by beginning her postdoctoral fellowship with Drs. Barbara Vanderhyden and David Cook at the Ottawa Hospital Research Institute, where she will continue to explore the interactions between ovarian cancer and the immune system.
“The Terry Fox New Investigator funding that was awarded to Dr. Boudreau was instrumental in enabling us to develop the technologies that led to our key discoveries, which have been crucial to my own success as a scientist,” says Dr. Nersesian. “I am eager to expand on the findings from my PhD work, utilizing a systems-based approach to further explore how ovarian cancer cells interact with various immune cell populations.”