Dr. Martin Cannon, of University of Arkansas for Medical Sciences (UAMS), is a 2021 recipient of OCRA’s Collaborative Research Development Grant. With his project, “Understanding and Targeting Myeloid Populations in Ovarian Cancer,” Dr. Cannon seeks to better understand the behavior of a type of immune cell that currently helps ovarian cancer tumors grow, in order to harness these same immune cells to fight ovarian cancer instead.
My initial scientific interest back in high school was genetics, from reading about Darwinian evolution and Mendelian genetics, but also going as far back as Aristotle’s De Generatione Animalium. That curiosity led me to study microbial and molecular genetics as an undergraduate at University College London, where I got my first exposure to immunology. In graduate school and postdoctoral training in immunology, I came to appreciate the huge impact genetics has on the adaptive immune system, through classic studies on MHC polymorphism and restriction of T cell responses, and the diversity of antibody responses. This fascinating intersection of genetics and immunology ultimately drove me to pursue research training in the immunology of viral infections and cancer.
In my earlier career, I worked on the immunology of Epstein-Barr virus-associated lymphoma, initially at the Scripps Research Institute and latterly at the University of Arkansas for Medical Sciences, so I had a natural interest in cancer immunology. Credit for my interest in ovarian cancer stems from a productive collaboration with Alessandro Santin, who is now Professor of Gynecologic Oncology at Yale University, which ultimately led to my current work on dendritic cell vaccination for treatment of ovarian cancer patients. Many studies from other investigators have shown that the immunopathology of ovarian cancer has a major impact on clinical outcomes. Notably, immune suppression in the ovarian tumor microenvironment is associated with poor clinical outcomes and increased mortality. From a clinical perspective, ovarian cancer has not been responsive to established immunotherapies, such as immune checkpoint inhibition with nivolumab or prembrolizumab, hence my current interest in research to circumvent tumor-associated immunosuppressive barriers and promote successful immunotherapy for ovarian cancer.
The immune system normally eliminates damaged or abnormal cells, much like it works to fight off infections caused by microbes, but cancer cells can trick the immune system into protecting the tumor and helping it to grow. Our project focuses on a type of immune cell called a macrophage, which is usually very good at eating and removing damaged cells. However, in ovarian cancer, macrophages suppress immune responses against the tumor and help the tumor to grow and spread. We will investigate new ways to change the behavior of macrophages in ovarian cancer, such that they help the immune system to attack and destroy abnormal tumor cells.
I am driven by the desire to advance laboratory studies to clinical trials for immunotherapy of ovarian cancer. We have recently published encouraging results from a Phase I clinical trial of dendritic cell vaccination for treatment of stage III/IV ovarian cancer. However, it is clear that we need to improve outcomes for immunotherapy of ovarian cancer through combinatorial approaches to combat tumor-associated immunosuppression. Our OCRA program grant will directly address this challenge through studies to target tumor-associated myeloid cells that play a pivotal role in blocking the efficacy of immunotherapy.
The last decade has seen a revolution in cancer treatment, such that immunotherapy through immune checkpoint inhibition has become a mainstay of clinical care for many types of cancer. Unfortunately, the success of immunotherapy has not extended to treatment of ovarian cancer, even though there is clear evidence that immune responses have a significant impact on clinical outcomes. My hope is that by taking a bimodal approach to treatment, aimed at stimulation of antitumor immunity through tumor vaccines or cellular therapies, combined with novel strategies to alleviate tumor-associated immune suppression, we may ultimately be able to achieve improved clinical outcomes and prolonged survival for ovarian cancer patients in clinical trials.
If you had the opportunity to personally thank someone from the OCRA community who supported your work, what would you say?
Support from an OCRA Collaborative Research Development Grant has given us the unique opportunity to take a multifaceted approach to a problem that we feel is crucial to the future success of immunotherapy for ovarian cancer. The cross-fertilization of ideas and strategies between our three research groups (Anil Sood at MD Anderson Cancer Center, Dan Powell at the University of Pennsylvania, and my laboratory at UAMS) will provide new insights into the function of myeloid cells in ovarian cancer in immune suppression and tumor growth. We anticipate that our OCRA-supported studies will have a significant impact for development of novel strategies to render the tumor microenvironment more responsive to immunotherapies such as tumor vaccines, cellular therapies and immune checkpoint inhibition. This collective effort arose from discussions at an OvaCure meeting held in Copenhagen in January 2020, but it would not have come to fruition without your personal support for the mission of OCRA, for which we are truly grateful.
See more OCRA-funded ovarian cancer immunotherapy research projects.