Frontiers in Immunology (Oct 2024)

Tertiary lymphoid structure-related score as a predictor for survival prognosis and immunotherapy response in head and neck squamous cell carcinoma

  • Fan Wu,
  • Fan Wu,
  • Haotian Cao,
  • Haotian Cao,
  • Siqi Ren,
  • Siqi Ren,
  • Jiaying Wu,
  • Jiaying Wu,
  • Xin Liu,
  • Xin Liu,
  • Qunxing Li,
  • Qiuping Xu,
  • Qiuping Xu,
  • Jiali Chen,
  • Jiali Chen,
  • Ruixin Wang,
  • Ruixin Wang,
  • Suling Chen,
  • Suling Chen,
  • Shijia Kuang,
  • Shijia Kuang,
  • Binbin Xia,
  • Yanyan Li,
  • Yanyan Li,
  • Liansheng Wang,
  • Jintao Li,
  • Bowen Li,
  • Bowen Li,
  • Jinsong Li,
  • Jinsong Li,
  • Tianjun Lan,
  • Tianjun Lan

DOI
https://doi.org/10.3389/fimmu.2024.1483497
Journal volume & issue
Vol. 15

Abstract

Read online

BackgroundSubstantial studies reveal that tertiary lymphoid structure (TLS) correlate with prognosis and immunotherapy response in various types of cancers. However, the predictive value of TLS, the specific immune cell subtype within TLS and their anti-tumor mechanisms remain unclear.MethodsBased on 23 TLS-related genes (TLSRGs), we utilized bioinformatics methods to construct a scoring system, named TLSscore. By integrating RNA and single-cell sequencing data, we assessed the utility of TLSscore in head and neck squamous cell carcinoma (HNSCC). Flow cytometric sorting was used to isolate specific T cells subtypes, in vivo and in vitro experiments were conducted to demonstrate its anti-tumor effects.ResultsThe TLSscore model was constructed and specific TLSscore-genes were found to consistently align with the spatial location of TLS. TLSscore has proven to be a robust predictive model for predicting survival prognosis, immune cell infiltration, somatic mutation and immunotherapy response. Notably, a specific PD1+CXCL13+CD8+T cell subtype was identified within TLS. Both in vivo and in vitro experiments demonstrated that PD1+CXCL13+CD8+T cell might represent a functional cell subtype exerting anti-tumor effects during the process of immune surveillance.ConclusionsOur study presents a predictive model for TLS, which can evaluate its presence and predicts survival prognosis and immunotherapy response in HNSSC patients. Additionally, we identify a specific subtype of T cells that might elucidate the mechanism of TLS function in anti-tumor activities. This T cell subtype holds the potential to be a prognostic marker and a target for adoptive cell therapy (ACT) in the future.

Keywords