Different Expression Characteristics of LAG3 and PD-1 in Sepsis and Their Synergistic Effect on T Cell Exhaustion: A New Strategy for Immune Checkpoint Blockade.
Front Immunol
; 10: 1888, 2019.
Article
in En
| MEDLINE
| ID: mdl-31440257
ABSTRACT
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 (P < 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 (P < 0.05). The proportion of coexpressing T cells was negatively correlated with the total number of lymphocytes (r = -0.653, P = 0.0003) and positively correlated with the SOFA score (r = 0.712, P < 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
T-Lymphocytes
/
Antigens, CD
/
Sepsis
/
Programmed Cell Death 1 Receptor
Type of study:
Observational_studies
/
Prognostic_studies
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Front Immunol
Year:
2019
Document type:
Article
Affiliation country:
China