As an important part of tumor microenvironment,neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis.Here we defined,at single-cell resolution,CD44-CxCR2-neutrophils as tumor-specific neutrophils(tsNeus)in both mouse and human gastric cancer(GC).We uncovered a Hippo regulon in neutrophils with unique YAP signature genes(e.g.,ICAM1,CD14,EGR1)distinct from those identified in epithelial and/or cancer cells.Importantly,knockout of YAP/TAz in neutrophils impaired their differentiation into CD54+tsNeus and reduced their antitumor activity,leading to accelerated GC progression.Moreover,the relative amounts of CD54+tsNeus were found to be negatively associated with GC progression and positively associated with patient survival.Interestingly,GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+tsNeus.Furthermore,pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC,with no significant inflammation-related side effects.Thus,our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus,opening a new possibility to develop neutrophil-based antitumor therapeutics.
目的 研究老年颅内动脉瘤术后颅内感染患者CD54、磷脂酶A2(PLA2)、丙二醛(MDA)对预后的影响。方法 选取2017年10月-2020年10月华中科技大学同济医学院附属梨园医院收治的282例行老年颅内动脉瘤手术患者,根据术后是否发生颅内感染分为感染组(n=40)、未感染组(n=242),比较两组术前、术后1 d、术后3 d CD54、PLA2、MDA,并比较感染组不同预后患者术前、术后1 d、术后3 d CD54、PLA2、MDA水平,并归纳颅内感染患者预后的影响因素,采用受试者工作特征(ROC)曲线及曲线下面积(AUC)分析各指标预测预后价值,比较不同CD54、PLA2、MDA水平者预后分布情况。结果 感染组术后1 d、术后3 d CD54、PLA2、MDA较术前、未感染组均升高(P<0.05);预后不良、良好患者术后1 d、术后3 d CD54、PLA2、MDA较术前升高,且预后不良患者术后1 d、术后3 d CD54、PLA2、MDA高于良好患者(P<0.05);术后1 d、术后3 d CD54、PLA2、MDA均与感染患者预后相关(P<0.05);术后1 d、术后3 d各指标联合预测预后不良的AUC值高于单一检测(P<0.05);CD54、PLA2、MDA高水平者预后不良发生率高于低水平者(P<0.05)。结论 老年颅内动脉瘤术后颅内感染患者CD54、PLA2、MDA明显异常升高,且与预后效果密切相关,可作为分子标志物协助临床治疗方案的制定与调整。
