Table 3.

Effects of DNMT inhibitors on the PD-(L)1 checkpoint

Drug	Effects on PD-(L)1 checkpoint	References
DAC	DAC increases PD-L1 expression in melanoma and malignant pleural mesothelioma cell lines.	(41,42)
	The mechanism leading to PD-L1 expression involves a DAC-induced hypomethylation of interferon-related genes IRF1/7 to restore PD-L1 level.	(43)
	A combination of DAC plus anti-PD-1 camrelizumab gave a better complete remission rate than camrelizumab alone in patients with relapsed/refractory Hodgkin’s lymphoma.	(44)
	Low-dose DAC enhances PD-1 blockade in colorectal cancer by remodulating the tumor microenvironment.	(45)
5-AZA	Synergistic combination of 5-AZA plus a PD-(L)1 inhibitor in hematological malignancies.	(46)
	5-AZA upregulates PD-1, PD-L1 and PD-L2 transcripts and protein in patients with AML/MDS; upregulation associated with drug resistance.	(47,48)
	The combination of 5-AZA and durvalumab (anti-PD-L1) provided no significant advantages compared to 5-AZA alone in patients with AML or high-risk MDS.	(49)
	The combination of 5-AZA and pembrolizumab (anti-PD-1) is safe, feasible and well tolerated by AML patients.	(50)
Guadecitabine (SGI-110)	Guadecitabine (plus ipilimumab) exhibits significant antitumor and immunomodulatory activity in advanced melanoma, increasing the number of CD8+, PD-1+ T cells in tumor.	(51)
	SGI-110 negatively regulates inhibitory accessory cells in the tumor microenvironment by decreasing PD-1-expressing T cells.	(52)
	In a mouse model of breast cancer, guadecitabine potentiated T-cell recruitment and enhanced antitumor immunity.	(53)