Tertiary lymphoid structure-related score as a predictor for survival prognosis and immunotherapy response in head and neck squamous cell carcinoma
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 o...
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Frontiers Media S.A.
2024-10-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1483497/full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Fan Wu |
| collection | DOAJ |
| description | 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. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-2dac23ac552043e3be0438ec4bf235b42025-08-20T01:47:50ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-10-011510.3389/fimmu.2024.14834971483497Tertiary lymphoid structure-related score as a predictor for survival prognosis and immunotherapy response in head and neck squamous cell carcinomaFan Wu0Fan Wu1Haotian Cao2Haotian Cao3Siqi Ren4Siqi Ren5Jiaying Wu6Jiaying Wu7Xin Liu8Xin Liu9Qunxing Li10Qiuping Xu11Qiuping Xu12Jiali Chen13Jiali Chen14Ruixin Wang15Ruixin Wang16Suling Chen17Suling Chen18Shijia Kuang19Shijia Kuang20Binbin Xia21Yanyan Li22Yanyan Li23Liansheng Wang24Jintao Li25Bowen Li26Bowen Li27Jinsong Li28Jinsong Li29Tianjun Lan30Tianjun Lan31Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaGuangdong 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, ChinaDepartment of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaGuangdong 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, ChinaDepartment of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaGuangdong 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, ChinaDepartment of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaGuangdong 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, ChinaDepartment of Stomatology, Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, ChinaDepartment of Stomatology, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, Guangdong, ChinaDepartment of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaGuangdong 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, ChinaMedical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, ChinaGuangdong 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, ChinaMedical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, ChinaDepartment of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaGuangdong 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, ChinaDepartment of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaGuangdong 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, ChinaDepartment of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaGuangdong 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, ChinaDepartment of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaDepartment of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaGuangdong 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, ChinaDepartment of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaDepartment of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaDepartment of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaGuangdong 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, ChinaDepartment of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaGuangdong 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, ChinaDepartment of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, ChinaGuangdong 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, ChinaBackgroundSubstantial 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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1483497/fulltertiary lymphoid structurehead and neck squamous cell carcinomaTLSRGsTLSscoreimmunotherapy |
| spellingShingle | 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 Tertiary lymphoid structure-related score as a predictor for survival prognosis and immunotherapy response in head and neck squamous cell carcinoma Frontiers in Immunology tertiary lymphoid structure head and neck squamous cell carcinoma TLSRGs TLSscore immunotherapy |
| title | Tertiary lymphoid structure-related score as a predictor for survival prognosis and immunotherapy response in head and neck squamous cell carcinoma |
| title_full | Tertiary lymphoid structure-related score as a predictor for survival prognosis and immunotherapy response in head and neck squamous cell carcinoma |
| title_fullStr | Tertiary lymphoid structure-related score as a predictor for survival prognosis and immunotherapy response in head and neck squamous cell carcinoma |
| title_full_unstemmed | Tertiary lymphoid structure-related score as a predictor for survival prognosis and immunotherapy response in head and neck squamous cell carcinoma |
| title_short | Tertiary lymphoid structure-related score as a predictor for survival prognosis and immunotherapy response in head and neck squamous cell carcinoma |
| title_sort | tertiary lymphoid structure related score as a predictor for survival prognosis and immunotherapy response in head and neck squamous cell carcinoma |
| topic | tertiary lymphoid structure head and neck squamous cell carcinoma TLSRGs TLSscore immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1483497/full |
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