Immunologic profile and prognostic significance of tumor-infiltrating lymphocytes in renal cell carcinoma.

Abstract

673 Background: Renal cell carcinoma (RCC) has been shown to be a genetically and morphologically heterogeneous cancer. As studies show the significance of tumor-infiltrating lymphocytes (TIL) in cancer, it is critical to examine how the phenotype of TILs manifests in RCC. Such analysis may help explain the role of the immune landscape in developing resistance and its contribution to the high treatment failure observed in immunotherapy for RCC. This study compares the immune phenotype of primary tumors, venous tumor thrombi (VTT), and metastases, as well as multiple sites within primary tumors, and investigates whether inter- and intra-tumoral immune heterogeneity is present in RCC. The association of TIL levels and clinical prognosis will also be assessed and compared with current RCC prognostic scores. Methods: Our cohort included 15 VTT and 6 metastases (3 adrenal, 2 bone, 1 liver) with 20 matched primary tumors, as well as 25 non-metastatic primary tumors. The RCC tissue was collected and digested into single cell suspensions. Suspensions were stained for TIL surface markers and processed using flow cytometry. The data was analyzed to capture %CD8+ and %CD4+ in total tumor. The %CD28+ and %PD1+ of CD8+ cells were measured to describe the co-stimulatory and co-inhibitory receptor expression, respectively. Clinical data was obtained to calculate the Mayo Stage, Size, Grade, and Necrosis (SSIGN) and UCLA Integrated Staging System (UISS) scores for each patient and to evaluate recurrence. Results: Immunologic concordance was observed in all measured parameters (%CD8+, %CD4+, %CD28+, and %PD1+) for primary tumors and VTT, for primary tumors and their metastases, and for different sites within 10 primary tumors. In our overall cohort, %CD8+ was found to be inversely associated with recurrence (p = 0.02). Furthermore, %CD8+ was not significantly associated with patient Mayo SSIGN and UISS scores. Conclusions: Despite the genetic and morphologic heterogeneity seen in RCC, immunologic concordance was observed for both inter- and intra-tumoral analysis. The association between %CD8+ and recurrence presents a novel and objective immune-based prognostic factor for RCC, independent of Mayo SSIGN and UISS scores.