Immune-based medicines are effective in treating and curing subsets of patients across multiple cancers. However, approximately 80% of patients across all cancers fail to respond to immune-based medicines. This lack of clinical benefit is particularly prevalent in aggressive forms of metastatic prostate cancer (MPC) that are resistant to hormonal therapies, where few objective responses to immune-based medicines have been observed.
The immune system is comprised of cells that can both promote and suppress the growth of the cancer. Our research has revealed that the microenvironment within MPC exhibits scarcity of immune cells. Furthermore, the sparse immune cells that reside within the microenvironment of MPC promote tumor growth and progression. Therefore, there is an urgent need to develop medicines that reprogram the tumor-promoting “bad” immune cells to create a more favorable environment, so the “good” immune cells can enter the tumor and kill cancer cells. The goal of our research is to identify and develop new medicines that can achieve this “switch” in the immune system, to enhance recognition and elimination of the most aggressive forms of prostate cancer. We will test these potential medicines in both mouse models of PC in the laboratory, and in patients with the most aggressive forms of MPC enrolled in clinical trials. Collectively, the findings stemming from this proposal will lead to a deeper understanding of the immune escape mechanisms that allow MPC to spread, and advance the clinical development of novel medicines to reinvigorate the body’s immune system to eradicate MPC.