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
复制标题
Atezolizumab 可减轻 PD-L1 阳性中性粒细胞引起的免疫抑制并提高脓毒症期间小鼠的存活率
DOI：
10.3892/mmr.2020.11783
复制
发表时间：
2021-02-01
影响因子：
3.4
通讯作者：
Zhang, Sen
中科院分区：
文献类型：
--
作者：
Chen, Jianxin;Chen, Ruiyuan;Zhang, Sen
阿替利珠单抗可减少多种癌症类型中由T淋巴细胞凋亡引起的免疫抑制。本研究旨在探讨该药物是否也能缓解脓毒症期间的免疫抑制。为此，建立了C57BL/6小鼠脓毒症模型。将小鼠随机分为三组：假手术组、盲肠结扎穿孔（CLP）组和阿替利珠单抗组。通过腹腔注射在体内给予阿替利珠单抗。评估中性粒细胞上程序性死亡配体 - 1（PD - L1）和T淋巴细胞上程序性死亡 - 1（PD - 1）的表达，并检测内毒素浓度、肠道通透性、回肠组织病理学评分以及紧密连接蛋白的表达，以确定每组的疾病程度。测定T淋巴细胞凋亡率以评估阿替利珠单抗在体内和体外对T淋巴细胞凋亡的影响。还记录生存时间以比较脓毒症期间小鼠的预后。在CLP组中，血液中在48、72和96小时以及骨髓中在24、48、72和96小时，PD - L1（+）中性粒细胞的比例与假手术组相比显著升高（P
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 in vivo 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 in vivo and in vitro. 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