Tertiary lymphoid structures critical for the prognosis of patients with cervical cancer

Abstract Cervical cancer (CC) is the most common female reproductive system tumor. However, the tertiary lymphoid structures (TLSs) associated with CC have not been well studied. This study aimed to develop a novel TLS-based signature to stratify the prognosis of patients with CC and predict the clinical outcomes. The data were obtained from the TCGA (n = 292) and GEO (n = 300) databases. We classified TLS subtypes (C1 and C2) of CC based on the TLSs-9 gene signature using unsupervised hierarchical clustering, with the C1 subtype having a worse prognosis than the C2 subtype. Regarding immune-related features, immune and stromal scores, immune checkpoint gene expression, and tumor mutation burden were significantly higher in C2 than in C1. We found higher infiltration ratios of memory B cells, CD8 + T cells, activated memory CD4 + T cells, and activated macrophages in C2. Patients with C1 were more sensitive to cisplatin, doxorubicin, bleomycin, vinorelbine, and imatinib than those with C2. The risk score model and prognostic nomogram constructed based on the TLS signature were significantly and positively correlated with the survival rate of patients with CC. The presence of TLSs provides new insights into the prognosis of patients with CC, contributing to the precise stratification and accurate treatment.