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  • Atezolizumab alleviates the immunosuppression induced by PD‑L1‑positive neutrophils and improves the survival of mice during sepsis.

Atezolizumab alleviates the immunosuppression induced by PD‑L1‑positive neutrophils and improves the survival of mice during sepsis.

Molecular medicine reports (2021-03-04)
Jianxin Chen, Ruiyuan Chen, Shaoxiong Huang, Bin Zu, Sen Zhang
ABSTRACT

Atezolizumab can reduce immunosuppression caused by T lymphocyte apoptosis in various cancer types. The current study aimed to investigate whether this drug can also alleviate immunosuppression during sepsis. For that purpose, a C57BL/6 mouse sepsis model was generated. Mice were randomly assigned to three groups: Sham, cecal ligation and puncture (CLP) and atezolizumab groups. Atezolizumab was administered <em>in vivo</em> by intraperitoneal injection. The expression of programmed death ligand‑1 (PD‑L1) on neutrophils and programmed death‑1 (PD‑1) on T lymphocytes was evaluated, and endotoxin concentration, intestinal permeability, ileum histopathological score and tight junction protein expression were assessed to determine the extent of disease in each group. The rate of T lymphocyte apoptosis was determined to assess the effects of atezolizumab on T lymphocyte apoptosis <em>in vivo</em> and <em>in vitro</em>. Survival times were also recorded to compare mouse prognosis during sepsis. In the CLP group, the proportion of PD‑L1+ neutrophils was significantly higher at 48, 72 and 96 h in blood, and at 24, 48, 72 and 96 h in bone marrow, compared with those of the sham group (P&lt;0.05). The proportion of PD‑1+ T lymphocytes was also upregulated at 72 h in blood. In the atezolizumab group, endotoxin concentration, intestinal permeability and ileum histopathological score were lower compared with those in the CLP group (P&lt;0.05), whereas the expression of claudin‑1 and occludin proteins on ileum was higher compared with that in the CLP group (P&lt;0.05). Both <em>in vivo</em> and <em>in vitro</em> experiments indicated that the rate of T lymphocyte apoptosis following atezolizumab treatment was lower compared with that in the CLP group (P&lt;0.05). Survival analysis demonstrated that mice in the atezolizumab group survived longer compared with those in the CLP group (P&lt;0.05). The current study demonstrated that treatment with atezolizumab may be an effective method for treating immunosuppression induced by sepsis.

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Fluorescein isothiocyanate–dextran, average mol wt 40,000