Research Paper Volume 16, Issue 8 pp 6898—6920

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

Guohai Xiong1,2, , Jinmei Shan1,2, , Qingguo Chong1,2, , Yueqing Cui1,2, ,

  • 1 Department of Gynaecology, Yancheng Third People’s Hospital, Yancheng 224008, China
  • 2 Department of Gynaecology, The Yancheng School of Clinical Medicine of Nanjing Medical University, Yancheng 224008, China

Received: November 1, 2023       Accepted: February 13, 2024       Published: April 17, 2024
How to Cite

Copyright: © 2024 Xiong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


CESC: cervical squamous carcinoma; TLS: tertiary lymphoid structure; TME: tumor microenvironment; TCGA: The Cancer Genome Atlas; GEO: Gene Expression Omnibus; scRNA-seq: single-cell RNA sequencing; PCA: principal component analysis; t-SNE: t-Distributed Stochastic Neighbor Embedding; DEG: differential expressed gene; ssGSEA: single-sample enrichment analysis; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genome; TMA: tissue microarray; IHC: immunohistochemistry; IRS: immunoreactivity score; CNV: copy number variation.