Objective:To investigate the expression of programmed cell death protein 1 (PD-1), programmed cell death ligand 1(PD-L1), and lymphocyte-activation gene 3(LAG-3) in different subsets of lymphocytes and their relationship with the immunologic imbalance in preeclampsia.Methods:We enrolled 25 cases of singleton pregnant women with preeclampsia who were delivered by cesarean section in the Shandong Provincial Hospital Affiliated to Shandong First Medical University from May 2019 to January 2020 as the preeclampsia group. According to the allocation ratio of 1∶1 matched for the date of cesarean section and pregnancy week at delivery, another 25 healthy singleton pregnant women underwent elective cesarean section were selected as the normal group. The decidua tissue was obtained during cesarean section. The expression levels of PD-1, PD-L1, and LAG-3 on decidual T cells, natural killer (NK), and natural killer T (NKT) cells were measured by flow cytometry and compared between the two groups using two independent samples- t test. Results:(1) The expression of PD-1 on decidual T cells and NK cells of the preeclampsia group were lower than those of the normal group (37.84±3.82 vs 57.02±3.89, t=3.529, P<0.001; 3.28±0.48 vs 5.69±0.99, t=2.184, P=0.034), but did not differ significantly in the expression on decidual NKT cells ( P=0.461). PD-L1 expression on decidual NK cells of preeclampsia group was lower than that of the normal group (0.60±0.11 vs 1.32±0.19, t=3.319, P=0.002), but showed no significant difference in the expression level on T cells and NKT cells (both P>0.05). The preeclampsia group was noted for a lower expression of LAG-3 on decidual T cells and NKT cells compared with the normal group (2.32±0.36 vs 4.09±0.67, t=2.335, P=0.024; 35.40±4.97 vs 56.27±4.49, t=3.282, P=0.002), while showed no significant difference in the expression level of NK cells ( P=0.112). Conclusions:The decreased expression of PD-1, PD-L1, and LAG-3 in the decidual lymphocyte subsets may be involved in the immunologic imbalance of preeclampsia through the over-activation of immunocytes at the maternal-fetal interface.

Hypoxia,a salient feature of solid tumors,is often associated with invasiveness,metastasis and resistance to anticancer drugs.The strategies including the use of oxygen-carriers based on hyperbaric oxygen and blood substitutes to transport oxygen into tumors or in situ generation of O2from the tumor microenvironment endogenous H2O2have been explored to relieve the tumor hypoxia and to improve therapeutic efficiency.In addi-tion,it is potential to design hypoxia-responsive nanocarriers based on tumor hypoxia microenvironment to deliver anticancer drugs to the targeted tumor site,thereby improve drug concentrations in targeted site,significantly increase the antitumor efficiency and reduce the side-effects of drugs.This review gives an overview of the advances in relieving tumor hypoxia and hypoxia-responsive nanocarriers for tumor to provide a reference for the research and development of new antitumor drugs.