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SELP(+) TEC:CD8(+) T 细胞交互作用与宫颈癌放疗疗效改善相关

英文原题:SELP(+) TEC:CD8(+) T cell crosstalk associates with improved radiotherapy efficacy in cervical cancer.

查看英文原题

SELP(+) TEC:CD8(+) T cell crosstalk associates with improved radiotherapy efficacy in cervical cancer.

PubMed 2025/02/03(内容时间) Mol Cancer Q1 · IF 42.2(JCR 2025)

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中文摘要

P-selectin(SELP)在肿瘤细胞中的表达已被认为可促进多种癌症的肿瘤进展和治疗耐药。然而,我们此前的研究发现SELP在宫颈癌(CC)内特定内皮细胞亚群中表达,并可能与抗癌免疫应答相关。

然而,SELP影响抗癌免疫及其参与CC放疗反应的确切机制仍不清楚。为填补这些空白,本研究分析了205例接受放疗的CC患者的肿瘤组织样本、8例患者42,159个细胞的scRNA-seq数据,以及187例接受放疗患者的bulk RNA测序数据。

结果显示,肿瘤内皮细胞(TECs)中SELP表达升高与接受放疗患者的生存结局改善显著相关。SELP高表达组表现出免疫相关通路的显著富集,同时上皮细胞增殖和血管生成通路的富集减少。

值得注意的是,该组显示CD8 + T细胞浸润增加,且包括ACKR1在内的趋化因子受体表达增强。此外,我们的数据提示SELP + TECs通过ACKR1-CCL5轴与CD8 + T细胞发生串扰,这与放疗疗效改善相关。

总之,这些发现强调了SELP + TEC:CD8 + T细胞通过ACKR1-CCL5通路相互作用在增强CC放疗反应中的关键作用。靶向这一串扰可能为减轻治疗耐药和改善患者生存提供新的治疗策略。

展开英文摘要原文

P-selectin (SELP) expression in tumor cells has been implicated in promoting tumor progression and treatment resistance across various cancers.

However, our prior study identified SELP expression in a specific subpopulation of endothelial cells within cervical cancer (CC) and potentially linked to anti-cancer immune response. The precise mechanisms by which SELP influences anti-cancer immunity and its involvement in radiotherapy response in CC, however, remain elusive. To address these gaps, this study analyzed tumor tissue samples from 205 CC patients undergoing radiotherapy, scRNA-seq data from 42,159 cells of eight patients, and bulk RNA-sequencing data from 187 radiotherapy-treated patients.

The results revealed that elevated SELP expression in tumor endothelial cells (TECs) was significantly correlated with improved survival outcomes in patients treated with radiotherapy. The SELP high group exhibited a prominent enrichment of immune-related pathways, coupled with a diminished enrichment in epithelial cell proliferation and angiogenesis pathways.

Notably, this group demonstrated increased infiltration of CD8 + T cells and enhanced expression of chemokine receptors, including ACKR1.

Furthermore, our data suggest that SELP + TECs engage in crosstalk with CD8 + T cells via the ACKR1-CCL5 axis, which is associated with improved radiotherapy efficacy.

In conclusion, these findings underscore the pivotal role of SELP + TEC:CD8 + T cell interactions through the ACKR1-CCL5 pathway in enhancing radiotherapy response in CC. Targeting this crosstalk may offer novel therapeutic strategies to mitigate treatment resistance and improve patient survival.

论文信息

作者
Huang Q、Yang W、Wang F、Huang R、Wang Q、Li X、Lei T、Yue S
第一作者单位
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, China.China
通讯作者单位
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, China. charles.liu@whu.edu.cn.China
期刊
Molecular cancer2025 Feb 3
原文标识
PubMed 39901166 · DOI 10.1186/s12943-025-02244-7