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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.

DOI:10.18632/aging.205733
PMID:38709170
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11087108/
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/a4dec04aeb96/aging-16-205733-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30c3/11087108/4b384e99f1ca/aging-16-205733-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30c3/11087108/a9b32ed6a515/aging-16-205733-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30c3/11087108/a4dec04aeb96/aging-16-205733-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30c3/11087108/4b384e99f1ca/aging-16-205733-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30c3/11087108/083a8cf8d9c4/aging-16-205733-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30c3/11087108/edde2aebd7bc/aging-16-205733-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30c3/11087108/64d46353649e/aging-16-205733-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30c3/11087108/a4dec04aeb96/aging-16-205733-g007.jpg

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本文引用的文献

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Tertiary lymphoid structures and B lymphocytes: a promising therapeutic strategy to fight cancer.三级淋巴结构和 B 淋巴细胞:一种有前途的抗癌治疗策略。
Front Immunol. 2023 Aug 9;14:1231315. doi: 10.3389/fimmu.2023.1231315. eCollection 2023.
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Genomic properties and clinical outcomes associated with tertiary lymphoid structures in patients with breast cancer.与乳腺癌患者三级淋巴结构相关的基因组特性和临床结局。
Sci Rep. 2023 Aug 19;13(1):13542. doi: 10.1038/s41598-023-40042-7.
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Tertiary lymphoid structures predict the prognosis and immunotherapy response of cholangiocarcinoma.
三级淋巴结构预测胆管癌的预后和免疫治疗反应。
Front Immunol. 2023 May 10;14:1166497. doi: 10.3389/fimmu.2023.1166497. eCollection 2023.
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The roles of tertiary lymphoid structures in chronic diseases.三级淋巴结构在慢性疾病中的作用。
Nat Rev Nephrol. 2023 Aug;19(8):525-537. doi: 10.1038/s41581-023-00706-z. Epub 2023 Apr 12.
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Density and maturity of peritumoral tertiary lymphoid structures in oesophageal squamous cell carcinoma predicts patient survival and response to immune checkpoint inhibitors.食管鳞状细胞癌中肿瘤周围三级淋巴结构的密度和成熟度可预测患者的生存和对免疫检查点抑制剂的反应。
Br J Cancer. 2023 Jun;128(12):2175-2185. doi: 10.1038/s41416-023-02235-9. Epub 2023 Apr 4.
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Maturation and abundance of tertiary lymphoid structures are associated with the efficacy of neoadjuvant chemoimmunotherapy in resectable non-small cell lung cancer.三级淋巴结构的成熟度和丰度与可切除性非小细胞肺癌新辅助化疗免疫治疗的疗效相关。
J Immunother Cancer. 2022 Nov;10(11). doi: 10.1136/jitc-2022-005531.
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