研究进展

肿瘤源性细胞外囊泡中 Serpin A1 货物支持中性粒细胞的促肿瘤偏倚

来源:Journal of extracellular vesicles · PMID 42969065 · DOI 10.1002/jev2.70385 · 来源:IMA 知识库《文献层·文献监控卡片》2026-11-05 期 · 全文级(file_id dAlZBwueyWSz,实际下载核验 1,395,640 B) · 全文已获取并通过三重归属校验

时间标签:数据日期 2026-11-05 · 生成时间 2026-11-05 05:30(Asia/Shanghai)| 检索窗口 PubMed edat 2026/11/02 – 2026/11/06 | 情报发生日期 2026-11-05

研究问题

Images were collected on Zeiss LSM 710 combined with ELYRA PS.1 Super‐resolution and TIRF (total internal reflection fluorescence) module using 100×, 1.46 NA Zeiss objective and GaASP detector (Carl Zeiss, Germany).;Fluorescence intensity was measured by flow cytometry as described above.2.26Treatment of Neutrophils With Soluble Recombinant Serpin A1To assess whether soluble, vesicle‐free Serpin A1 is sufficient to reproduce the effects of td‐sEVs, freshly isolated neutrophils (4 × 106 cells/mL) were incubated with recombinant human Serpin A1 protein (Novus Biologicals, cat# 1268‐PI‐010) at a final concentration of 1 µg/mL in RPMIc medium, or with PBS as a negative control, for 18 h at 37°C, 5% CO2.;Considering the presence of serpins in sEVs released by cancer cells, we aimed to evaluate the importance of those proteins in the reprogramming of neutrophils.FIGURE 4Tumour‐derived serpinhi sEVs induce EMT through neutrophil reprogramming.

方法

In patients with solid malignancies, including head and neck cancer (HNC), neutrophil counts in blood and tumour tissue are frequently increased and correlate with adverse clinical outcomes (Pylaeva et al. 2022; Trellakis et al. 2011; Albrengues et al. 2018; Anselmi et al. 2022), reflecting a shift from early anti‐tumoural activity toward a pro‐tumoural, immunosuppressive state as advanced disease (Andzinski et al. 2016).;The clinical characteristics of the enrolled participants are presented in Figure 1A,B and Figure S1.;The patients were scheduled for surgical tumour resection and consented to blood collection for research purposes at the Otorhinolaryngology, Head and Neck Surgery Department of the University Hospital of Duisburg‐Essen, Essen, Germany.

核心结论

(F) Analysis of the open‐access database GSE6585827 demonstrates an association of Serpin A1 overexpression in tumour tissue as a predictor of poor prognosis in HPV‐negative HNC.;Data are shown as individual values with a median. *p < 0.05, ***p < 0.005.These findings reveal that activation of neutrophils in vitro by td‐sEVs mirrors the proteomic alterations observed in neutrophils from HNC patients.In line with the proteomics data, we observed elevated neutrophil activation and degranulation after education with td‐sEVs, as shown by the downregulation of CD62L and increased expression of CD11b and CD66b (Figure 3E).;The obtained results demonstrate that the changes of neutrophil phenotype and activity during cancer progression are attributed to td‐sEVs, rather than soluble factors released by cancer cells to plasma or tumour microenvironment.3.4Tumour‐Derived sEV‐Educated Neutrophils Induce EMT in Cancer Cells via Serpin A1To functionally assess properties of sEV‐reprogrammed neutrophils, we incubated sEV‐primed neutrophils with cancer cells (Figure 4A).

局限

However, significant higher particle quantities were recovered in sEV samples from plasma of HNC patients than in those from healthy donors (Figure 1G).;However, neutrophils primed by serpinhi sEVs were significantly less efficient than cells stimulated by serpindef sEVs (Figure 5E).To evaluate whether this phenomenon applies to the situation observed in cancer patients, we analysed tumour‐supportive properties of neutrophils reprogrammed by plasma td‐sEVs.;However, direct pharmacological inhibition of serpins remains challenging.

对本项目的价值

中高价值:属「干细胞 / 部分重编程与再生」方向;干细胞 / 再生 / 重编程栏目可用作本项目文献库与综述素材。 | 价值分 3.3/5(★★★☆☆)

全文来源

PubMed PMC JATS(正文 81,388 字符,题名指纹 0.85,已过 PubMed PMCID 官方关联 + 题名指纹 + 正文长度归属校验)

原文题录

  • 中文题名:肿瘤源性细胞外囊泡中 Serpin A1 货物支持中性粒细胞的促肿瘤偏倚
  • 英文标题:Serpin A1 Cargo Within Tumour-Derived Extracellular Vesicles Supports Pro-Tumoural Bias of Neutrophils in Cancer.
  • 期刊与标识:Journal of extracellular vesicles · PMID 42969065 · DOI 10.1002/jev2.70385 · PMC PMC13725528

A 级证据分级:A 级(同行评议人体研究)

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