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

被引:0
作者
Li, Xia [1 ]
Cheng, Yanmei [2 ]
Ji, Mei [2 ]
Liu, Junqi [1 ]
Zhao, Zhao [2 ]
Zhao, Qitai [3 ,4 ]
机构
[1] Zhengzhou Univ, Dept Radiat Oncol, Affiliated Hosp 1, Zhengzhou 450052, Henan, Peoples R China
[2] Zhengzhou Univ, Affiliated Hosp 1, Dept Gynecol & Obstet, Zhengzhou 450052, Henan, Peoples R China
[3] Zhengzhou Univ, Affiliated Hosp 1, Biotherapy Ctr, Zhengzhou 450052, Henan, Peoples R China
[4] Zhengzhou Univ, Affiliated Hosp 1, Canc Ctr, Zhengzhou 450052, Henan, Peoples R China
基金
中国博士后科学基金;
关键词
Cervical squamous cell carcinoma; Concurrent chemoradiotherapy; Recurrence; CXCL13(+) T cells; Cell communication; Random forest model; CANCER; CHEMOTHERAPY;
D O I
10.1007/s00262-025-04083-3
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 x 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.
引用
收藏
页数:18
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