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

## TL;DR

Tertiary lymphoid structures in cervical cancer are linked to better outcomes and improved response to immunotherapy.

## Contribution

This study is the first to systematically analyze TLS in cervical squamous carcinoma and its association with immune response and prognosis.

## Key findings

- TLS presence correlates with better prognosis and activation of immune pathways in cervical cancer.
- TLS is associated with reduced tumor cell proliferation and a less malignant tumor state.
- Tumors with TLS show increased sensitivity to immunotherapy in independent cohorts.

## 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.