Background: Although the programmed death 1 (PD-1)/programmed death-ligand 1 
(PD-L1) inhibitors have markedly changed the strategies of cancer treatment, 
most patients with advanced non-small cell lung cancer (NSCLC) do not respond to 
PD-1/PD-L1 monotherapy. Epigenetic drugs have been hypothesized to possess the 
potential to sensitize PD-1/PD-L1 inhibitors. Case Presentation: Three patients 
with advanced metastatic NSCLC failed to respond to first-line systemic therapy 
and had a low tumor mutation burden, low tumor neoantigen burden, low 
microsatellite instability, and HLA loss of heterozygosity according to their 
target lesion biopsies, all of which were considered unfavorable factors for 
PD-1/PD-L1 blockage. However, all three patients responded to low-dose 
decitabine, an epigenetic drug, in combination with camrelizumab (anti-PD-1 
antibody), with only controllable adverse events, indicating that low-dose 
decitabine can sensitize PD-1/PD-L1 inhibitors. Summary: We report a novel 
therapy with low-dose decitabine plus camrelizumab for advanced NSCLC on the 
basis of successful treatment of three patients, emphasizing the potential of 
epigenetic drugs to regulate PD-1/PD-L1 inhibitors in advanced NSCLC.