Compounding such findings were studies that assessed activators/inhibitors of SP140/TLR4 signaling in glioblastoma and clear cell renal cell carcinoma (ccRCC), which showed that when TLR4 is activated, PD-L1 levels are upregulated, allowing for immune evasion and immune escape from checkpoint blockade [67]. Here, SP140 is linked to nonpapillary renal cell carcinoma.