Background: Loss of co-stimulatory molecules by CD8 T-cells is associated with reduced proliferative and cytotoxic function in chronic viral infections, aging, and cancer. Several lines of evidence suggest that a more functional immune system is associated with better patient outcomes, and improved response to immunotherapy in a range of different cancers. For this reason, understanding the features of a patient that predict the loss of T-cell function is important. In this study we characterized how co-stimulatory molecules are expressed by T-cells in the tumors of RCC patients. Additionally, we characterized how distant sites of metastasis differ from the primary tumor, and finally, we evaluated levels of blood inflammatory markers (BIMs) to predict how co-stimulatory on CD8+ TILs change. Methods: Patients that underwent resection of primary and/or metastatic RCC at Emory University Hospital were prospectively enrolled in the study. Levels of pre-op BIMs were retrieved from medical records. A portion of resected tumor tissue was analyzed by flow cytometry to measure percentage of CD8+ cells expression of the co-stimulatory molecules, ICOS, CD27, CD40L, CD226, CD28, and CD2. A composite co-stimulatory score (co-stim score) was calculated by taking a weighted average of the number of co-stimulatory receptors expressed per cell. BIMs were correlated with CD28 expression and co-stim score. Expression of co-stimulatory receptors was compared between patient-matched primary tumor and metastatic tumor pairs. Results: We found that by CD8 T-cells in tumors often lost co-stimulatory molecules. Furthermore, albumin and Hgb both had a strong positive correlation with CD28 expression and overall co-stim score, while WBC, Plt, neutrophil-lymphocyte ratio (NLR), ESR, and CRP was negatively correlated. Expression of co-stimulatory receptors did not differ significantly between primary tumor and metastatic tumor pairs suggesting that a systemic effect controlled TIL phenotype rather than site specific factors. Conclusions: Our data show that BIMs have the potential to predict the immunologic phenotypes of cytotoxic TILs in RCC noninvasively.