Research: 2018 – Ottawa (Ardolino)

Project Title:
Analysis of the innate lymphocyte landscape in prostate cancer.
Michele Ardolino, Ottawa Hospital Research Institute/University of Ottawa
I have a long-standing interest in the immune system and in the immune response to tumors. During my training, I have focused on how the immune response is kept in check by cell intrinsic and cell extrinsic mechanisms. My laboratory is currently investigating how to empower the immune system to fight tumors, with a particular emphasis on prostate cancer. During my career, I have published my results in high profile peer reviewed scientific journals and contributed to the preparation of several reviews. A Ride for Dad grant in 2017 was essential to generate data that were recently published in the Journal of Clinical Investigation (Hsu et al., 2018) and laid the bases to a funded CIHR application. We keep being interested in understanding the immune response in the prostate and are asking for support to generate preliminary data to dissect the role and functions of a new subsets of immunoregulatory cells, ILCs, in the prostate. Our established technical expertise allows us to confidently approach these in vivo studies as well as the cellular and molecular processes outlined in the proposal. I established my group only 2 years ago, and I built a team of very motivated and talented young researchers that I am leading with enthusiasm. Thanks to the excellent results obtained by my trainees, and the support and the network at the OHRI, I have presented my work in many international scientific meetings and I was invited to give talks in several Canadian Universities as a guest lecturer. Over the years I was always able to attract funding to cover my salary and I was able to secure grants to fund our research. I believe we have all the expertise and enthusiasm required to successfully carry out the proposed project.

Project Abstract:
The immune system is composed by a myriad of cells that have different roles in protecting the body against infections and cancer. In recent years, an increase understanding of the immune system has brought to the development of new cancer therapies that take advantage of the ability of the immune system to kill tumor cells. These immunotherapies have been successful in several tumor types, but not in prostate cancer. We believe that one reason why immunotherapy is not as effective in prostate cancer is that some immuneregulatory mechanisms are in place in the prostate that are currently not known. Here, we will analyze a population of immune cells, called innate lymphoid cells, that have been shown to have great immunomodulatory potential. By increasing our understanding of innate lymphoid cells in the prostate, we believe we will be able to design new and more effective immunotherapies for prostate cancer.
Scientific Abstract:
Prostate cancer has been described as an immunologically cold tumor, with limited infiltration of effector cells, such as CD8 T cells and Natural Killer cells, and lack of potent anti-tumor inflammation. The reduced therapeutic efficacy of many forms of immunotherapy in prostate cancer, including checkpoint blockade and oncolytic virotherapy, has been partially attributed to the coldness of the prostate microenvironment. However, the mechanisms that regulate the immunological landscape of the prostate tumor environment are not entirely known. We hypothesize that a population of innate immune cells, namely innate lymphoid cells, plays a major role in regulating the inflammatory context in the prostate. Here, we will characterize the innate lymphoid cell populations in the prostate of mice injected or not with tumor cells, and in response to immunotherapy. We anticipate that the insights from this study will allow to begin a larger project with the goal to modulate the activity of innate lymphoid cells and potentiate immunotherapy.
Impact on prostate cancer patients:
The clinical implications of this project are two-fold: i) we will characterize new players of the immune response to prostate cancer; and,
ii) we will set the stage to ameliorate prostate cancer immunotherapy in future studies.