Altering the sPD-L1 and exoPD-L1/mPD-L1 balance in NSCLC cells through CDK12 inhibition using small molecules like THZ531 might impact the effectiveness of PD-1/PD-L1 immunotherapy, and suggests a potential link to DDR and HR pathway-directed therapy. The gene discussed is CDK12; the disease is non-small cell lung carcinoma.