Dr. Jeanette Boudreau is the scientific director at the Beatrice Hunter Cancer Research Institute and an associate professor at Dalhousie University in Halifax, who has held a Terry Fox New Investigator Award since 2019. As her project wraps up, we spoke with her to further understand the impact the award has had on her research and scientific career.
TFRI: CAN YOU PLEASE REMIND US OF WHAT THE MAJOR GOALS OF YOUR PROJECT WERE?
JB: One of the main goals of our lab is to see if Natural Killer cells (NK cells), which are important players in our immune system and have proven to have cancer-fighting potential, can be used as or in immunotherapies for ovarian cancer. To do that, we first needed to understand how NK cells interact with tumours and map the signals that could be exploited by NK cells to recognize and attack high-grade serous carcinoma (HGSC). This last part was a big portion of my Terry Fox New Investigator Award.
TFRI: WHAT ARE SOME OF THE MAJOR FINDINGS/ADVANCES YOU'VE BEEN ABLE TO MAKE AS PART OF YOUR NI PROJECT?
JB: One of our major breakthroughs has been identifying a panel of markers that can be used to define NK cells clearly, differentiating them from closely related cells like monocytes or innate lymphoid cells. With this, we can clarify confusion that has existed around the role of NK cells in ovarian cancer.
- We designed a multiplex immunohistochemistry staining panel to ascertain the role of NK cells in ovarian cancer. With this, we can measure infiltration not only of NK cells, but also of macrophages and T cells, two cell subtypes that are already known to predict good prognosis for patients with ovarian cancer. Using digital pathology and machine learning (backed by a board-certified pathologist), we segregated cells and tissues, and devised strategies to quantify how they interact and relate spatially, basically creating a map of where these cells are located and how they interact with each other in the tumour microenvironment. We then identified patterns of cell clustering in that map to predict outcomes for patients with ovarian cancer.
In a parallel set of studies, we have been investigating how the genetic changes that exist in ovarian cancer predict their interactions with immune cells, particularly NK cells.
- There are major mutations identified in high- grade serous ovarian cancer: BRCA1, BRCA2, TP53 and PTEN to name a few. With animal models and bioinformatics analysis, we have begun to understand that these mutations correspond with different interactions with immune mechanisms. Collectively, the interpretation of this is that bioinformatics and biopsy assessments could set the stage for effective (NK-based) immunotherapies for ovarian cancer. In fact, they suggest that immunotherapies will need to be tailored to the specific immune landscapes of these tumours.
TFRI: WHAT FORESEEABLE IMPACT COULD THESE DISCOVERIES HAVE ON OVARIAN CANCER PATIENTS?
JB: Existing immunotherapies have only been effective in a small subset of patients with ovarian cancer. Our work is revealing the pieces that need to be in place to potentially use NK cells to effectively target this deadly disease. With an increased understanding, we can devise strategies to affect the best immune response in each patient (or identify patients unlikely to benefit from immunotherapy, and direct different approaches to treatment).
In general, and certainly for NK cell-based treatments, immunotherapies are less toxic than traditional approaches to treatment (i.e., chemotherapy and radiation). Ovarian cancer, particularly HGSC, has a high rate of recurrence and ultimately leads to death in about half of all patients. Identifying how immunotherapy can be integrated into the treatment of patients may enhance quality of life, or perhaps lead to better disease management. The tools to do this are already in place: we are identifying how best to apply these tools for the best outcomes in patients.
TFRI: LET’S SWITCH AWAY FROM THE SCIENCE FOR A MOMENT: WHAT IMPACT HAS THE NEW INVESTIGATOR AWARD HAD ON YOUR CAREER?
The TFRI NI award gave me the opportunity to establish collaborations and build a network that continues to expand, lasting beyond the tenure of the award.
JB: I’m Canadian and completed all my studies here, up until my post-doc. I went to the United States to study at that point, and then returned home when I started my laboratory. This put me in an interesting position: I didn’t have as extensive a Canadian network as someone domestically trained might have had, and my lab was in Halifax, away from the major centres where immunotherapy is being done.
We have established workflows and working groups that we are now using to apply for further funding from TFRI and other agencies, and my exposure as a Terry Fox New Investigator has given me the confidence to start building cell therapy programs in Halifax.