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Speckle-type POZ protein (SPOP) and CDK4/6 pathway. Cyclin D-CDK4/6 complex phosphorylates wild type-SPOP (WT-SPOP) which results in ubiquitination and destruction of programmed death ligand 1 (PD-L1). CDK4/6 inhibitors are able to prevent this ubiquitination and also increase T-cell activation and tumor infiltrating lymphocytes (TIL’s). Cancer mutated SPOP allows for increased PD-L1 expression of tumor cells and decreases tumor infiltrating lymphocytes.
