Posted September 22, 2015
Brad H. Nelson, Ph.D., British Columbia Cancer Agency
High-grade serous ovarian cancer is a difficult to treat and deadly disease. Despite this, one-fourth of patients live for many years after treatment. It is known that the immune system can play an important role in patient survival. In particular, a high concentration of killer T-cells expressing the cluster of differentiation 8 (CD8) surface protein, a type of white blood cell that can fight infections and cancer, correlates with increased survival. However, these killer T cells do not work alone in this process. They require supportive B cells and T helper cells that express FoxP3 to be effective. Understanding the immune response to ovarian cancer and how it can be harnessed to improve patient outcomes is the goal of FY11 OCRP Teal Expansion Award recipient Dr. Brad Nelson at the British Columbia Cancer Agency.
Dr. Nelson and his team have shown previously that Interleukin-2 (IL-2) receptor proteins are expressed on the surface of T cells and respond to the cytokine IL-2, mediating key functions of the immune response. The CD25 protein is the alpha subunit of the IL-2 receptor that is expressed on regulatory T cells, involved in immune suppression, and effector T-cells, involved in immune activation, making its exact role in ovarian cancer unclear. In this study, Dr. Nelson and colleagues further examined the phenotype and prognostic significance of CD25+ tumor infiltrating lymphocytes (TIL) in high-grade serous carcinomas. Using multi-parameter flow cytometry and immunohistochemistry techniques, Dr. Nelson discovered two TIL subsets that potentially explain the contradictory observations of CD25 in cancer. TIL that express CD25, CD4, and FoxP3 compromised a majority of the CD4+ TIL in many patients. This subtype was found to be phenotypically similar to regulatory T cells and associated with a poor patient prognosis. A second subgroup of TIL expressing CD25 and CD4, but not FoxP3, was identified and had a strong association with patient survival despite displaying an exhausted phenotype.
Based on these findings, Dr. Nelson plans to further investigate the role of CD4+CD25+FoxP3- TIL in spontaneous tumor immunity. This work could ultimately lead to the use of this TIL subset as effector cells for the immunotherapy treatment of serous ovarian cancer patients to increase the rates of survival.