Abstract 2700: CD8 T-cell infiltration into renal tumors requires a supportive antigen-presenting niche

Abstract

Abstract Background: Tumor infiltrating immune cells have a clear prognostic benefit in many tumor types. Immune variables have independently improved prognostication in various cancer types, with tumor-infiltrating lymphocytes (TILs) more accurately predicting patient survival than currently employed methods. This has been shown using the Immuno-score, which predicts disease progression in colorectal cancer based on CD8 T cell infiltration. Many recent studies have also highlighted similar observations in other cancers, including breast cancer, lung cancer, and melanoma. These observations raise the question of whether the level of CD8 T cell infiltration into renal cell tumors may also predict patient survival, and more fundamentally, why some patients may mount a strong immune response to their tumors and others do not. Methods: Tumor tissue was collected from 68 renal cell carcinoma (RCC) patients undergoing surgery at Emory University Hospital. Patients had a minimum follow up time of 24 months. Intraoperative tumor samples were processed and analyzed by flow cytometry and immunofluorescence. Results: The proportion of CD8 TILs, measured by flow cytometry, was found to vary widely in RCC patients. This CD8 T cell response is independent of standard risk assessment tools, tumor size, pathology, and patient demographics. Significantly, an increasing percent of tumor CD8 T cells is associated with improved cancer-specific survival in these patients, and this association is particularly strong in a small cohort of stage III patients. The phenotype and functional capacity of TILs were examined, and presence of a stem-like CD8 T cell—that can proliferate and differentiate—was required to generate a strong anti-tumor Tcell response. When this stem-like T cell is lost, there is a poor anti-tumor immune response and patients experience progressive disease. Flow cytometry analysis revealed that the number of dendritic cells in the tumor correlates with T cell infiltration, and immunofluorescence image analysis showed that stem-like T cells reside in areas of high antigen-presenting cell density. Tumors with poor T cell infiltration lack APC density, suggesting that an antigen presenting niche is required for a strong T cell response. Conclusions: Measuring CD8 T cell infiltration in RCC predicts cancer-specific survival, particularly in patients with advanced disease. As this patient population is one for whom improved prognostication is a critical clinical goal, this study represents an opportunity to inform future prognostic measures and to direct reduction or intensification of therapy. The T cell response was found to be maintained by a population of cells, which harbor both proliferative and differentiation capacity. These stem-like cells require a supportive niche inside the tumor in order to persist, and without this support, the T cell response collapses, resulting in disease progression. Citation Format: Caroline S. Jansen, Nataliya Prokhnevska, Viraj A. Master, Jennifer W. Carlisle, Mehmet A. Bilen, Adriana M. Reyes, Haydn T. Kissick. CD8 T-cell infiltration into renal tumors requires a supportive antigen-presenting niche [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2700.