Keynote Speaker: Microbiome Mediated Mechanisms of Immune Therapy Failure for Ovarian Cancer with Live Q&A

Patients with high-grade serous ovarian cancer will often initially respond to surgery and chemotherapy, with approximately 80% exhibiting recurrence and developing chemotherapy resistance. There is a significant need for alternate therapies capable of overcoming therapy resistance and reducing mortality associated with this disease. Tumor-infiltrating T cells correlate with increased survival and delayed recurrence in patients with advanced ovarian cancer. Despite this, treatment strategies to harness/reinvigorate T cell activity against ovarian tumors have largely been ineffective with overall dismal clinical performance. These studies emphasize the need for complementary therapies capable of overcoming resistance to checkpoint therapy, enhancing anti-tumor T cell responses, and improving patient outcomes. One strategy to overcome resistance to immune checkpoint blockade is to reprogram myeloid cells within the tumor microenvironment, given the central role that myeloid cells have in the control of anti-tumor immunity, tumor growth, and response to immune therapies. To date, studies have primarily focused on targeting or countering tumor-associated mechanisms known to impair anti-tumor function of myeloid cells, resulting in limited clinical success. Reasons for the lack of clinical success could be due to the inability of current therapeutic strategies to inhibit host-intrinsic factors that drive failure of immune checkpoint blockade. Unfortunately, little is known about host-intrinsic mechanisms that mitigate success of immune checkpoint blockade. Here, we will describe work from our lab that has identified a host-intrinsic mechanism leading to failure of checkpoint blockade that is mediated by interactions between immune cells and the host microbiota, exploring potential new therapeutic strategies designed to mitigate the negative effects of the host microbiome on anti-tumor immune function for ovarian cancer.

Learning Objectives: 

1. Discuss the barriers for ovarian cancer that are impairing immune therapy response in patients.

2. Summarize different mechanisms whereby the host microbiome can impact immune responses against tumors.

3. Discuss how Toll-Like Receptor expression on immune cells can impact function and identity in solid tumors.