It is now accepted that changes in the normal cells that constitute the tumor microenvironment (TME) play important roles in determining cancer progression and ultimate outcome. We and others have established that an immune signature, and more recently that the ability of CD8+ T cells to infiltrate the tumor bed, are correlated with good outcome in triple negative breast cancer. Importantly, since the cytotoxic effector functions of CD8+ T cells are mainly contact-dependent, the tumor microenvironment may act to inhibit access to the epithelial tumor bed, leading to uncontrolled tumor growth. Therefore, in order to determine the role that the TME plays on mediating the entry of CD8+ T cells into the epithelial tumor bed, our group performed laser-capture microdissection to separate the tumor epithelial compartment from the surrounding tumor-associated stroma from the primary tumor of 56 triple negative breast cancer patients and followed by gene expression profiling. Our aims are to provide clinical validation of predicted CD8+ T cell localisation based on our bioinformatic analysis, test our predictions that the identified stroma signature correlates with CD8+ T cell retention in other cohort of TN breast cancer patients and develop suitable markers of this stroma, and develop a muliplex based assay integrating CD8+ T cell localisation with stromal markers suitable for a retrospective study to validate predictions with outcome. Using gene expression profiling, our data have identified a canonical gene expression signature which correlates with retention of CD8+ T cells in the stroma and poor outcome. Thus, our results demonstrate that gene expression analysis of clinical triple negative breast cancer samples can predict the location of CD8+ T cells within the tumor and in turn the outcome.
Citation Format: Mathieu Gigoux, Tina Gruosso, Nicholas Bertos, Sadiq Saleh, Atilla Omeroglu, Hong Zhao, Margarita Souleimanova, Sarkis Meterissian, Michael Hallett, Morag Park. The immunological environment in triple negative breast cancer; impact on clinical outcomes towards a prognostic clinical test. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr A69.
- ©2015 American Association for Cancer Research.