Single-cell RNA sequencing analysis reveals a lack of CXCL13+ T cell subsets associated with the recurrence of cervical squamous cell carcinoma following concurrent chemoradiotherapy.

Abstract

Concurrent chemoradiotherapy (CCRT) is the standard treatment for advanced cervical cancer, but tumor recurrence within 3-5 years remains a significant challenge. In this study, using 10 × single-cell sequencing, we constructed a cellular atlas of the tumor microenvironment from six CSCC patients, including three with recurrence and three without, prior to CCRT. We analyzed cellular subsets, focusing on T cells, myeloid cells and cancer associated fibroblasts (CAFs), and their interactions within the tumor. Key findings revealed that CXCL13⁺ T cell subsets were significantly increased in non-recurrent tumors and acted as major signal senders. In recurrent tumors, FOXP3⁺ and IL2RA⁺ Tregs were the primary mediators of cell communications. CXCL13⁺ CD8⁺ T cells interacted with SPP1⁺ tumor-associated macrophages (TAMs) in non-recurrent tumors, while in recurrent tumors, they interacted with CD163⁺ TAMs. Moreover, in recurrent tumor tissues, this subset demonstrates a preferential interaction with MMP3⁺ CAFs. The study also identified five genes (PDCD1, CXCL13, TOX, RGS1, and ALOX5AP) based on CXCL13⁺ T cell signature to construct predictive models for recurrence, with the random forest model showing the best performance. This study provides new insights into recurrence mechanisms in CSCC and suggests that increasing CXCL13⁺ T cells could be a potential therapeutic strategy.