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与宫颈鳞状细胞癌中增强的抗肿瘤免疫和良好预后相关的三级淋巴结构。

Tertiary lymphoid structures associated with enhanced anti-tumor immunity and favorable prognosis in cervical squamous carcinoma.

机构信息

Department of Gynaecology, Yancheng Third People’s Hospital, Yancheng 224008, China.

Department of Gynaecology, The Yancheng School of Clinical Medicine of Nanjing Medical University, Yancheng 224008, China.

出版信息

Aging (Albany NY). 2024 Apr 17;16(8):6898-6920. doi: 10.18632/aging.205733.

Abstract

BACKGROUND

Cervical squamous carcinoma (CESC) is the main subtype of cervical cancer. Unfortunately, there are presently no effective treatment options for advanced and recurrent CESC. Tertiary lymphoid structures (TLSs) are clusters of lymphoid cells that resemble secondary lymphoid organs; nevertheless, there is no summary of the clinical importance of TLS in CESC.

METHODS

A large set of transcriptomic and single-cell RNA-sequencing (scRNA-seq) datasets were used to analyze the pattern of TLS and its immuno-correlations in CESC. Additionally, an independent in-house cohort was collected to validate the correlation between TLS and TME features.

RESULTS

In the current study, we found that the presence of TLS could predict better prognosis in CESC and was correlated with the activation of immunological signaling pathways and enrichment of immune cell subpopulations. In addition, TLS was associated with reduced proliferation activity in tumor cells, indicating the negative correlation between TLS and the degree of malignancy. Last but not least, in two independent immunotherapy cohorts, tumors with the presence of TLS were more sensitive to immunotherapy.

CONCLUSION

Overall, TLS is related to an inflamed TME and identified immune-hot tumors, which could be an indicator for the identification of immunological features in CESC.

摘要

背景

宫颈鳞状细胞癌(CESC)是宫颈癌的主要亚型。不幸的是,目前对于晚期和复发性 CESC 尚无有效的治疗方法。三级淋巴结构(TLS)是类似次级淋巴器官的淋巴样细胞簇;然而,目前尚无 TLS 在 CESC 中的临床重要性的综述。

方法

使用大量转录组和单细胞 RNA 测序(scRNA-seq)数据集来分析 CESC 中 TLS 的模式及其免疫相关性。此外,还收集了一个独立的内部队列来验证 TLS 与 TME 特征之间的相关性。

结果

在本研究中,我们发现 TLS 的存在可以预测 CESC 的预后更好,并且与免疫信号通路的激活和免疫细胞亚群的富集相关。此外,TLS 与肿瘤细胞增殖活性降低相关,表明 TLS 与恶性程度呈负相关。最后但同样重要的是,在两个独立的免疫治疗队列中,存在 TLS 的肿瘤对免疫治疗更敏感。

结论

总体而言,TLS 与炎症性 TME 相关,并确定了免疫热肿瘤,这可能是识别 CESC 中免疫特征的指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30c3/11087108/4b384e99f1ca/aging-16-205733-g001.jpg

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