Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Front Immunol. 2024 Oct 18;15:1483497. doi: 10.3389/fimmu.2024.1483497. eCollection 2024.
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.
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, and experiments were conducted to demonstrate its anti-tumor effects.
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 PD1CXCL13CD8T cell subtype was identified within TLS. Both and experiments demonstrated that PD1CXCL13CD8T cell might represent a functional cell subtype exerting anti-tumor effects during the process of immune surveillance.
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.
大量研究表明，三级淋巴结构（TLS）与多种癌症的预后和免疫治疗反应相关。然而，TLS 的预测价值、TLS 内特定免疫细胞亚群及其抗肿瘤机制仍不清楚。
基于 23 个 TLS 相关基因（TLSRGs），我们利用生物信息学方法构建了一个评分系统，命名为 TLSscore。通过整合 RNA 和单细胞测序数据，我们评估了 TLSscore 在头颈部鳞状细胞癌（HNSCC）中的应用。采用流式细胞分选术分离特定的 T 细胞亚群，并进行实验以证明其抗肿瘤作用。
构建了 TLSscore 模型，并且特定的 TLSscore 基因与 TLS 的空间位置一致。TLSscore 被证明是一种强大的预测模型，可以预测生存预后、免疫细胞浸润、体细胞突变和免疫治疗反应。值得注意的是，TLS 内鉴定出一种特定的 PD1CXCL13CD8T 细胞亚群。和实验均表明，PD1CXCL13CD8T 细胞可能代表一种具有抗肿瘤作用的功能细胞亚群，在免疫监视过程中发挥作用。
本研究提出了一种 TLS 的预测模型，可评估其存在，并预测 HNSCC 患者的生存预后和免疫治疗反应。此外，我们鉴定出一种特定的 T 细胞亚群，可能阐明了 TLS 在抗肿瘤活性中的功能机制。该 T 细胞亚群有望成为未来预后标志物和过继细胞治疗（ACT）的靶点。
