SMAD3 and non-small cell lung carcinoma: In non-small cell lung cancer (NSCLC), BET inhibition with JQ1 and OTX015 disrupts the BRD4-SMAD3 transcriptional axis that drives inhibitory receptor expression on NK cells enhancing NK-cell cytotoxicity and immune-checkpoint molecules (51), whereas in neuroblastoma, JQ1 reduces tumor susceptibility by downregulating ligands for NKG2D and DNAM-1, though the precise mechanisms remain less defined (87).