Our gene expression analyses show induction of inflammatory pathways in tRCC, including IFN-γ response, IL-6/JAK/STAT3, TLR signaling, immunoglobulin-mediated phagocytosis, systemic lupus erythematosus, NK cell–mediated cytotoxicity, and allograft rejection. Here, IL6 is linked to renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusions.