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

Front Immunol. 2024 Oct 18:15:1483497. doi: 10.3389/fimmu.2024.1483497. eCollection 2024.

Abstract

Background: Substantial 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.

Methods: Based 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.

Results: The 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.

Conclusions: Our 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: TLSRGs; TLSscore; head and neck squamous cell carcinoma; immunotherapy; tertiary lymphoid structure.

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Female
  • Head and Neck Neoplasms* / genetics
  • Head and Neck Neoplasms* / immunology
  • Head and Neck Neoplasms* / mortality
  • Head and Neck Neoplasms* / therapy
  • Humans
  • Immunotherapy* / methods
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Mice
  • Prognosis
  • Squamous Cell Carcinoma of Head and Neck* / genetics
  • Squamous Cell Carcinoma of Head and Neck* / immunology
  • Squamous Cell Carcinoma of Head and Neck* / mortality
  • Squamous Cell Carcinoma of Head and Neck* / therapy
  • Tertiary Lymphoid Structures* / immunology
  • Tumor Microenvironment / immunology

Substances

  • Biomarkers, Tumor

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by Science and Technology Program of Guangzhou (Grant No. 202102010144); the National Natural Science Foundation of China (Grant No. 82272788, 82072990, 82102755 and 82303758); the Guangdong Science and Technology Department (Grant No. 2024A1515012876, 2023B1212060013, 2020B1212060018, 2021A1515012355 and 2017A030311011); the Guangdong Basic and Applied Basic Research Foundation (Grant No. 2019A1515110662 and 2023A1515110704); the Medical Scientific Research Foundation of Guangdong Province (Grant No. A2023351); the Youth Project of Basic and Applied Basic Research Foundation of Guangdong Province (Grant No. 2021A1515110828); the China Postdoctoral Science Foundation funded project (Grant No. GZC20242069); CSCO-Meck Cancer Research Fund (Grant No. Y-MSDZD2022-0459).