Abstract A49: Investigating the expression of inhibitory surface molecules in ovarian cancer tumor-infiltrating lymphocytes.

Abstract

Abstract Ovarian cancer causes more deaths than any other cancer of the female reproductive system. However, novel therapies, including immunotherapy are now being utilized to treat this cancer. In addition, efforts have been made to identify and evaluate the subsets of cells within the tumor environment that correspond with patient overall survival. Although the presence of intraepithelial CD3+ T cells and CD8+ T cells have been correlated with patient survival and CD137, a co-stimulatory molecule, has been identified as a biomarker for tumor-reactive cells, studies have not thoroughly investigated the phenotype of the T cells, specifically the CD4+, CD8+, and CD137+ subsets. In our study, we used a multi-parameter flow cytometry to measure inhibitory molecules, Th1 cytokines, and the effector phenotype in the T-cell subsets. We observed that the CD4+ and CD8+ T cells found within the tumor environment express inhibitory receptors, very limited Th1 cytokine producing cells and a decreased expression of Granzyme B within the CD8+ subset. The CD137+ population also expressed inhibitory molecules, but was still able to exhibit an effector phenotype and comprise Th1 cytokine producing cells. In conclusion, using multi-parameter flow cytometry enabled us to investigate the expression of inhibitory molecules on the CD4+, CD8+, and CD137+ subsets and measure their effector phenotype. We found that the T cells express many inhibitory receptors and this may hinder their ability to become optimal effector cells that maintain tumor control. However, future studies utilizing antibodies that block these inhibitory receptors may increase the T cells' ability to exhibit an increased effector phenotype and contain more Th1 cytokine producing cells. Citation Format: Jessica Chacon, Tori Yamamoto, Thomas Garrabrant, Gabor Kari, Andrew Best, Qunrui Ye, Daniel Powell, Jr. Investigating the expression of inhibitory surface molecules in ovarian cancer tumor-infiltrating lymphocytes. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr A49.