The impairment of immunity characterized by T cell exhaustion is the main cause of death in patients with sepsis after the acute phase. Although PD-1 blockade is highly touted as a promising treatment for improving prognosis, the role of PD-1 plays in sepsis and particularly its different roles in different periods are still very limited. A recent study revealed LAG3 can resist the therapeutic effect of PD-1 blockade in tumor, which inspired us to understand their role in sepsis. We enrolled 26 patients with acute sepsis from 422 candidates using strict inclusion criteria. Follow-up analysis revealed that the expression levels of PD-1 were rapidly increased in the early stage of sepsis but did not change significantly as infection continued ( < 0.05). However, the expression of LAG3 was contrary to that of PD-1. Compared with LAG3 or PD-1 single-positive T cells, T cells coexpressing LAG3 and PD-1 were significantly exhausted ( < 0.05). The proportion of coexpressing T cells was negatively correlated with the total number of lymphocytes ( = -0.653, = 0.0003) and positively correlated with the SOFA score ( = 0.712, < 0.0001). In addition, the higher the proportion of coexpressing T cells was, the longer the hospital stay and the higher the mortality. These results showed that LAG3 and PD-1 had a potential synergistic effect in regulating the gradual exhaustion of T cells in sepsis, which seriously affected the clinical prognosis of patients. Therefore, LAG3 and PD-1 double-positive T cells are an important indicator for immunity detection and prognostic evaluation. In the future, precision therapy may pay more attention to the different expression patterns of these two molecules.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693426PMC
http://dx.doi.org/10.3389/fimmu.2019.01888DOI Listing

Publication Analysis

Top Keywords

lag3 pd-1
20
pd-1
10
cell exhaustion
8
pd-1 blockade
8
proportion coexpressing
8
coexpressing cells
8
lag3
7
sepsis
7
cells
6
expression
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!