
Dr Rachael Zemek: Raine BrightSpark Fellow
Leveraging the surgical wound healing immune response to stimulate local cancer eradication
Raine Priming Grant
$244,360.00
2022 - 2023
Telethon Kids Institute, The University of Western Australia
Dr Rachael Zemek, a child health researcher, undertook her Raine Priming Grant at the Telethon Kids Institute which focused on optimizing immunotherapy treatment to help combat cancers including sarcoma. Her research focused on identifying the specific time-dependent events that trigger tumor-specific T cell responses following surgical resection of tumours, and the optimal timing for initiating immunotherapy to achieve the highest response in combatting cancer. T cells, integral to our immune system, play a crucial role in defending the body against infections and cancer.
The front-line treatment for many solid cancers is surgical resection. Even with intensive chemotherapy, many patients will have recurrence of their cancer. It was known that surgery is a major immunological event, however, it was not known how surgery impacts remaining cancer or how it may influence current anti-cancer treatments such as immune checkpoint therapy. Dr Zemek found that following surgery, there is a rapid, but transient inflammatory response, in conjunction with an influx of an immune cell called neutrophils into the tumour area.
Dr Zemek explained, “I have characterized, for the first time, the effect of surgery-induced wound healing on cancer cells. I devised a model of surgical resection, that mimics the patient situation of residual tumour after surgery. Analysis of tumours over a time-course post-surgery identified a short window of opportunity for immunogenic therapeutic intervention. Astoundingly, by simply moving the day of surgery to shortly after the initiation of immune checkpoint therapy, we could drastically improve the response from 10% to 70% complete response. I therefore have compelling data that surgery can alter the response to immunotherapy. A better understanding of these treatments and how they interact may help inform clinicians about the optimal timing of immunotherapies and combinations to improve patient outcomes. These findings will be the basis for identifying therapeutic targets to boost the local wound healing response to increase response to immune checkpoint therapy, enabling more patients, particularly those with a high chance of relapse, to benefit.”
She continued, “The Raine Priming Grant allowed me to lead my own research project, turning an idea with basic proof of concept into an area of research with the potential to improve health outcomes. This was invaluable as an early career researcher, which has allowed me to grow into my own field, resulting in senior author publications, an invitation to publish in Nature Reviews Cancer and invitations to speak at national conferences. I also was able to supervise 1 PhD and 3 Honours students on this project to grow as a leader. As a result, I was offered an exciting and rewarding fellowship at the Fred Hutchinson Cancer Centre in Seattle (USA) to work in the laboratory of A/Prof. Evan Newell who is a globally renowned immunologist. I was also awarded a highly competitive NHMRC investigator grant which I will commence in 2026.”