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<p>Tertiary lymphoid structures (TLSs) are essential for promoting immune responses against tumours. However, the impact of TLS score and its maturation stage on the prognosis of colorectal cancer (CRC) patients has not yet been clarified. The aim of this study was to investigate the relationship between TLS score and its maturation stage and CRC prognosis through a retrospective study. In this study, firstly, high TLS score (≥0.752) was found to be a favourable prognostic factor for the survival of CRC patients using the TCGA database (HR = 0.381, 95% CI = 0.222 ~ 0.656). Secondly, CCL19, CCL21, and CXCL13 were found to be differential genes in the high and low TLS score groups in combination with several databases, and their main function was to chemotaxis TLS maturation. Subsequently, immunohistochemical staining was used to clarify the stage of TLS maturation in 76 clinical samples and to investigate its impact on patients’ survival prognosis. Finally, the validation of TNFRSF17 gene function was completed by cellular experiments. Analysis of the clinical samples showed that patients with higher early TLS (E-TLS) density had shorter survival than those with lower density (<i>P</i> = 0.016). High E-TLS density may be an independent risk factor for CRC (HR = 6.40, 95% CI = 1.82 ~ 22.55). However, the density of secondary follicular-like TLS did not show a significant prognostic effect in this study. In conclusion, patients with high TLS scores had longer survival, higher expression of immune checkpoint genes, and higher expression of TNFRSF17, which promotes T-cell infiltration and adhesion, but highly aggregated E-TLS may hamper patients’ survival prognosis.</p>

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Impact of tertiary lymphoid structure scores and their stage of maturation on prognosis of colorectal cancer patients

  • 期刊论文

  • 发表日期：

    2025年7月28日

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  • Si Shen,
  • Ran Sun,
  • Tian Wang,
  • Danfang Zhang,
  • Na Che,
  • Xiao Wang,
  • Nan Zhao

摘要

Tertiary lymphoid structures (TLSs) are essential for promoting immune responses against tumours. However, the impact of TLS score and its maturation stage on the prognosis of colorectal cancer (CRC) patients has not yet been clarified. The aim of this study was to investigate the relationship between TLS score and its maturation stage and CRC prognosis through a retrospective study. In this study, firstly, high TLS score (≥0.752) was found to be a favourable prognostic factor for the survival of CRC patients using the TCGA database (HR = 0.381, 95% CI = 0.222 ~ 0.656). Secondly, CCL19, CCL21, and CXCL13 were found to be differential genes in the high and low TLS score groups in combination with several databases, and their main function was to chemotaxis TLS maturation. Subsequently, immunohistochemical staining was used to clarify the stage of TLS maturation in 76 clinical samples and to investigate its impact on patients’ survival prognosis. Finally, the validation of TNFRSF17 gene function was completed by cellular experiments. Analysis of the clinical samples showed that patients with higher early TLS (E-TLS) density had shorter survival than those with lower density (P = 0.016). High E-TLS density may be an independent risk factor for CRC (HR = 6.40, 95% CI = 1.82 ~ 22.55). However, the density of secondary follicular-like TLS did not show a significant prognostic effect in this study. In conclusion, patients with high TLS scores had longer survival, higher expression of immune checkpoint genes, and higher expression of TNFRSF17, which promotes T-cell infiltration and adhesion, but highly aggregated E-TLS may hamper patients’ survival prognosis.