Pre-immunotherapy alters stereotactic ablative radiotherapy-induced systemic T cell responses in early-stage NSCLC
Abstract Background Stereotactic ablative radiotherapy (SABR) is thought to activate T cell responses in patients with cancer, leading to its combination with immunotherapy and chemotherapy for treatment of non-small-cell lung cancer (NSCLC). Here, we aimed to provide a high-resolution transcriptomi...
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| Format: | Article |
| Language: | English |
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Springer
2025-02-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-024-03935-8 |
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| author | Chao Liu Yanjuan Chen Xiaohui Li Zhijie Bai Meilin Jiang Dongsheng Sheng Wenxue Zou Rui Huang Qingyu Huang Fuhao Wang Jingyang Zhu Huiru Sun Bing Liu Zongcheng Li Bing Sun |
| author_facet | Chao Liu Yanjuan Chen Xiaohui Li Zhijie Bai Meilin Jiang Dongsheng Sheng Wenxue Zou Rui Huang Qingyu Huang Fuhao Wang Jingyang Zhu Huiru Sun Bing Liu Zongcheng Li Bing Sun |
| author_sort | Chao Liu |
| collection | DOAJ |
| description | Abstract Background Stereotactic ablative radiotherapy (SABR) is thought to activate T cell responses in patients with cancer, leading to its combination with immunotherapy and chemotherapy for treatment of non-small-cell lung cancer (NSCLC). Here, we aimed to provide a high-resolution transcriptomic profiling of the systemic T cell response following SABR, with or without preceding immunotherapy/chemotherapy. Methods We conducted single-cell RNA and T cell receptor (TCR) sequencing of T cells from peripheral blood of seven patients with early-stage NSCLC taken pre- and post-SABR without or with prior immunotherapy and chemotherapy (icSABR). Other flow cytometry, single-cell RNA-seq data and bulk RNA-seq data were used to validate the results. Results We uncovered distinct T cell response patterns induced by these treatments: while terminal effector CD8+ T cells showed increased cytotoxic and inhibitory scores, and upregulated immune-activated pathways post-SABR, the reverse responses occurred post-icSABR. Furthermore, the proportion of large T cell clones increased and single clone decreased post-SABR, while the opposite was seen post-icSABR. Of note, both SABR and icSABR largely changed TCR clonotypes, which were mainly large clones post-SABR but single clone post-icSABR, and predominantly from terminal effector CD8+ T cells and T helper cells, respectively. Conclusions These findings reveal a complex interplay between SABR and immunotherapy, with potentially valuable implications for treatment strategies involving SABR and immunotherapy to induce systemic T cell responses for tumor eradication in patients with NSCLC. |
| format | Article |
| id | doaj-art-c227a3c2c4f74ac2829d8abd6c7e66b7 |
| institution | Kabale University |
| issn | 1432-0851 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-c227a3c2c4f74ac2829d8abd6c7e66b72025-02-02T12:26:25ZengSpringerCancer Immunology, Immunotherapy1432-08512025-02-0174311810.1007/s00262-024-03935-8Pre-immunotherapy alters stereotactic ablative radiotherapy-induced systemic T cell responses in early-stage NSCLCChao Liu0Yanjuan Chen1Xiaohui Li2Zhijie Bai3Meilin Jiang4Dongsheng Sheng5Wenxue Zou6Rui Huang7Qingyu Huang8Fuhao Wang9Jingyang Zhu10Huiru Sun11Bing Liu12Zongcheng Li13Bing Sun14Department of Radiation Oncology, Peking University First HospitalDepartment of Geriatrics and Division of Rheumatology and Research, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital)Department of Medical Oncology, Peking University First HospitalState Key Laboratory of Experimental Hematology, Institute of Hematology, Fifth Medical Center of Chinese PLA General HospitalKey Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan UniversityDepartment of Thoracic Surgery, Fifth Medical Center of Chinese PLA General HospitalDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical SciencesDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical SciencesDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical SciencesDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical SciencesDepartment of Radiation Oncology, Fifth Medical Center of Chinese PLA General HospitalDepartment of Radiation Oncology, Fifth Medical Center of Chinese PLA General HospitalState Key Laboratory of Experimental Hematology, Institute of Hematology, Fifth Medical Center of Chinese PLA General HospitalState Key Laboratory of Experimental Hematology, Institute of Hematology, Fifth Medical Center of Chinese PLA General HospitalDepartment of Radiation Oncology, Fifth Medical Center of Chinese PLA General HospitalAbstract Background Stereotactic ablative radiotherapy (SABR) is thought to activate T cell responses in patients with cancer, leading to its combination with immunotherapy and chemotherapy for treatment of non-small-cell lung cancer (NSCLC). Here, we aimed to provide a high-resolution transcriptomic profiling of the systemic T cell response following SABR, with or without preceding immunotherapy/chemotherapy. Methods We conducted single-cell RNA and T cell receptor (TCR) sequencing of T cells from peripheral blood of seven patients with early-stage NSCLC taken pre- and post-SABR without or with prior immunotherapy and chemotherapy (icSABR). Other flow cytometry, single-cell RNA-seq data and bulk RNA-seq data were used to validate the results. Results We uncovered distinct T cell response patterns induced by these treatments: while terminal effector CD8+ T cells showed increased cytotoxic and inhibitory scores, and upregulated immune-activated pathways post-SABR, the reverse responses occurred post-icSABR. Furthermore, the proportion of large T cell clones increased and single clone decreased post-SABR, while the opposite was seen post-icSABR. Of note, both SABR and icSABR largely changed TCR clonotypes, which were mainly large clones post-SABR but single clone post-icSABR, and predominantly from terminal effector CD8+ T cells and T helper cells, respectively. Conclusions These findings reveal a complex interplay between SABR and immunotherapy, with potentially valuable implications for treatment strategies involving SABR and immunotherapy to induce systemic T cell responses for tumor eradication in patients with NSCLC.https://doi.org/10.1007/s00262-024-03935-8SABRNon-small-cell lung cancerImmunotherapySingle-cell RNA sequencingImmune response |
| spellingShingle | Chao Liu Yanjuan Chen Xiaohui Li Zhijie Bai Meilin Jiang Dongsheng Sheng Wenxue Zou Rui Huang Qingyu Huang Fuhao Wang Jingyang Zhu Huiru Sun Bing Liu Zongcheng Li Bing Sun Pre-immunotherapy alters stereotactic ablative radiotherapy-induced systemic T cell responses in early-stage NSCLC Cancer Immunology, Immunotherapy SABR Non-small-cell lung cancer Immunotherapy Single-cell RNA sequencing Immune response |
| title | Pre-immunotherapy alters stereotactic ablative radiotherapy-induced systemic T cell responses in early-stage NSCLC |
| title_full | Pre-immunotherapy alters stereotactic ablative radiotherapy-induced systemic T cell responses in early-stage NSCLC |
| title_fullStr | Pre-immunotherapy alters stereotactic ablative radiotherapy-induced systemic T cell responses in early-stage NSCLC |
| title_full_unstemmed | Pre-immunotherapy alters stereotactic ablative radiotherapy-induced systemic T cell responses in early-stage NSCLC |
| title_short | Pre-immunotherapy alters stereotactic ablative radiotherapy-induced systemic T cell responses in early-stage NSCLC |
| title_sort | pre immunotherapy alters stereotactic ablative radiotherapy induced systemic t cell responses in early stage nsclc |
| topic | SABR Non-small-cell lung cancer Immunotherapy Single-cell RNA sequencing Immune response |
| url | https://doi.org/10.1007/s00262-024-03935-8 |
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