Tumor cytokine profile of renal cell carcinoma patients

Abstract PurposeRenal cell carcinoma (RCC) accounts for 90% of all renal cancers and is considered highly immunogenic. Although many studies have reported the circulating peripheral cytokine profiles, the signatures between the tumor tissue and matching healthy adjacent renal tissue counterparts have not been explored. We aimed to comprehensively investigate the cytokine landscape of RCC tumors and its correlation between the amount and phenotype of the tumor infiltrating lymphocytes (TILs).Experimental Design We analyzed the secretion of 42 cytokines from the tumor (n=50) and adjacent healthy kidney tissues (n=24) with a Luminex-based assay. We further explored the differences between the tissue types, as well as correlated the findings with clinical data and detailed immunophenotyping of the TILs. ResultsUsing an unsupervised clustering approach, we observed distinct differences in the cytokine profiles between the tumor and adjacent renal tissue samples. The tumor samples clustered into three distinct profiles based on the cytokine expressions: high (53.2% of the tumors), intermediate (25.5%), and low (21.3%). Most of the tumor cytokines positively correlated with each other, except for IL-8 that showed no correlation with any of the measured cytokine expressions. Furthermore, the quantity of lymphocytes in the tumor samples analyzed with flow cytometry positively correlated with the chemokine-family of cytokines, IP-10 and MIG. Positive correlations were also observed between CD4+, CD8+ T cell PD-1 expressions and IL-8, suggesting a suppressive role of the chemotactic cytokine, even in T cell inflamed tumors. ConclusionsOur study highlights the distinct cytokine profiles in RCC and provides insights to potential biomarkers for the treatment of RCC.