Table 5.

Effects of anthracycline drugs on the PD-(L)1 checkpoint

Drug	Effects on PD-(L)1 checkpoint	References
DOX	DOX promotes expression of PD-L1 in osteosarcoma cell lines and clinical tissue samples. DOX inhibits proliferation of CD8+ T lymphocytes and their enhanced apoptosis. The use of an anti-PD-L1 antibody reversed the effect.	(122)
	DOX-induced upregulation of PD-L1 observed in bone marrow stromal cells in mice and in lymphoma patients, leading to T-cell exhaustion and impairment of T-cell functions.	(116)
	Downregulation of cell surface expression of PD-L1 in vitro and in vivo after DOX treatment. Cellular redistribution.	(123)
Doxil (pegylated liposomal DOX)	Doxil synergizes with anti-PD-1 mAbs, decreasing the percentage of tumor-infiltrating Tregs. In combination with anti-PD-L1, Doxil increases the percentage of tumor-infiltrating CD8+ T cells, in a tumor model.	(124)
Epirubicin (EPI)	EPI upregulates PD-L1 expression in subtypes of TNBC cell lines and patient samples.	(125)
	EPI decreases PD-L1 expression in the TNBC cell line MDA-MB-231 that strongly expresses PD-L1.	(126)
	The reduction of the expression of PD-L1 in hepatocellular carcinoma cells upon treatment with the cyclooxygenase-2 inhibitor celecoxib augments the therapeutic efficacy of EPI.	(127)
IDA	IDA can be combined with anti-PD-1 nivolumab to treat patients with newly diagnosed AML or high-risk MDS.	(24)