Abstract: Programmed death 1 （PD1） and its ligand （PDL1） can inhibit the proliferation and function of T and B cells by regulating cellular signaling pathways and epigenetic modifications. In the past decade， immune checkpoint blockades， such as inhibitors against PD1／PDL1，have received surprising clinical response in a variety of malignant tumors. However， the subsequent primary and acquired resistance has become a new problem， which not only influences longlasting response of PD1／PDL1 blockade therapy， but also limits its wide application in clinic. This paper will make a review on the related mechanisms of the regulation of PD1／PDL1 pathway and the resistance to PD1／PDL1 blockade therapy.

Key words: Programmed cell death 1／programmed cell death 1 ligand 1（PD1／PDL1）, Drug resistance, Epigenetic modifications, Tumor microenvironment