Landscape of the Peripheral Immune Response Induced by Intraoperative Radiotherapy Combined with Surgery in Early Breast Cancer Patients
Abstract A comprehensive analysis of the immune response triggered by intraoperative radiation therapy (IORT) remains incomplete. In this study, single‐cell RNA sequencing and single‐cell T cell receptor sequencing are conducted on peripheral blood mononuclear cells (PBMCs) from patient with early‐s...
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202308174 |
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| author | Danian Dai Xuerui Li Hongkai Zhuang Yun Ling Lezi Chen Cheng Long Jinhui Zhang Yunjie Wang Yuehua Li Hailin Tang Bo Chen |
| author_facet | Danian Dai Xuerui Li Hongkai Zhuang Yun Ling Lezi Chen Cheng Long Jinhui Zhang Yunjie Wang Yuehua Li Hailin Tang Bo Chen |
| author_sort | Danian Dai |
| collection | DOAJ |
| description | Abstract A comprehensive analysis of the immune response triggered by intraoperative radiation therapy (IORT) remains incomplete. In this study, single‐cell RNA sequencing and single‐cell T cell receptor sequencing are conducted on peripheral blood mononuclear cells (PBMCs) from patient with early‐stage breast cancer before and after IORT. Following IORT combined with surgery (defined as IORT+Surgery), PBMC counts remained stable, with increased proportions of T cells, mononuclear phagocytes, and plasma cells, and a reduction in neutrophil proportions. The cytotoxic score of CD8Teff_GZMK cells increased significantly post‐IORT. Communication between CD8Teff_GZMK cells and other immune cells via MIF_CD74 and MIF_TNFRSF14 is decreased after IORT. cDCs showed an upregulation of the MCH II signaling pathway, while memory B cells exhibited enhanced activation of the B cell pathway. T cell clones expanded significantly after treatment. IORT+Surgery demonstrated the ability to partially suppress the anti‐tumor effects of neutrophils. Flow cytometry analysis and co‐culture experiments are utilized to delve deeper into the functional alterations in T cells. IORT+Surgery significantly enhanced T cell cytotoxic activity. Blockade of PD‐1 of post‐IORT PBMCs shows higher T‐cell activity than that of pre‐IORT PBMCs. This research highlights IORT's impact on immune cells, offering insights for targeting immune responses in breast cancer. |
| format | Article |
| id | doaj-art-9fb1dee934f64694a156a794701c5b86 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-9fb1dee934f64694a156a794701c5b862025-01-09T11:44:45ZengWileyAdvanced Science2198-38442025-01-01121n/an/a10.1002/advs.202308174Landscape of the Peripheral Immune Response Induced by Intraoperative Radiotherapy Combined with Surgery in Early Breast Cancer PatientsDanian Dai0Xuerui Li1Hongkai Zhuang2Yun Ling3Lezi Chen4Cheng Long5Jinhui Zhang6Yunjie Wang7Yuehua Li8Hailin Tang9Bo Chen10Department of Plastic and Peripheral Vascular Surgery Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou Guangdong 510080 ChinaDepartment of Breast Cancer Cancer Center Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou Guangdong 510080 ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat‐sen Memorial Hospital Sun Yat‐Sen University Guangzhou Guangdong 510120 ChinaDepartment of Breast Surgery The Second Affiliated Hospital of Guangzhou Medical University Guangzhou Guangdong 510260 ChinaDepartment of Plastic and Peripheral Vascular Surgery Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou Guangdong 510080 ChinaDepartment of Pathology Yueyang Maternal Child Health‐Care Hospital Yueyang Hunan 414000 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐Sen University Cancer Center Guangzhou Guangdong 510060 ChinaSchool of Medicine Hunan University of Chinese Medicine Changsha Hunan 410208 ChinaDepartment of Oncology, The First Affiliated Hospital Hengyang Medical School University of South China Hengyang Hunan 421001 ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐Sen University Cancer Center Guangzhou Guangdong 510060 ChinaDepartment of Breast Cancer Cancer Center Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University Guangzhou Guangdong 510080 ChinaAbstract A comprehensive analysis of the immune response triggered by intraoperative radiation therapy (IORT) remains incomplete. In this study, single‐cell RNA sequencing and single‐cell T cell receptor sequencing are conducted on peripheral blood mononuclear cells (PBMCs) from patient with early‐stage breast cancer before and after IORT. Following IORT combined with surgery (defined as IORT+Surgery), PBMC counts remained stable, with increased proportions of T cells, mononuclear phagocytes, and plasma cells, and a reduction in neutrophil proportions. The cytotoxic score of CD8Teff_GZMK cells increased significantly post‐IORT. Communication between CD8Teff_GZMK cells and other immune cells via MIF_CD74 and MIF_TNFRSF14 is decreased after IORT. cDCs showed an upregulation of the MCH II signaling pathway, while memory B cells exhibited enhanced activation of the B cell pathway. T cell clones expanded significantly after treatment. IORT+Surgery demonstrated the ability to partially suppress the anti‐tumor effects of neutrophils. Flow cytometry analysis and co‐culture experiments are utilized to delve deeper into the functional alterations in T cells. IORT+Surgery significantly enhanced T cell cytotoxic activity. Blockade of PD‐1 of post‐IORT PBMCs shows higher T‐cell activity than that of pre‐IORT PBMCs. This research highlights IORT's impact on immune cells, offering insights for targeting immune responses in breast cancer.https://doi.org/10.1002/advs.202308174breast cancerintraoperative radiotherapyperipheral immune responsesingle‐cell RNA sequencingsingle‐cell T cell receptor sequencing |
| spellingShingle | Danian Dai Xuerui Li Hongkai Zhuang Yun Ling Lezi Chen Cheng Long Jinhui Zhang Yunjie Wang Yuehua Li Hailin Tang Bo Chen Landscape of the Peripheral Immune Response Induced by Intraoperative Radiotherapy Combined with Surgery in Early Breast Cancer Patients Advanced Science breast cancer intraoperative radiotherapy peripheral immune response single‐cell RNA sequencing single‐cell T cell receptor sequencing |
| title | Landscape of the Peripheral Immune Response Induced by Intraoperative Radiotherapy Combined with Surgery in Early Breast Cancer Patients |
| title_full | Landscape of the Peripheral Immune Response Induced by Intraoperative Radiotherapy Combined with Surgery in Early Breast Cancer Patients |
| title_fullStr | Landscape of the Peripheral Immune Response Induced by Intraoperative Radiotherapy Combined with Surgery in Early Breast Cancer Patients |
| title_full_unstemmed | Landscape of the Peripheral Immune Response Induced by Intraoperative Radiotherapy Combined with Surgery in Early Breast Cancer Patients |
| title_short | Landscape of the Peripheral Immune Response Induced by Intraoperative Radiotherapy Combined with Surgery in Early Breast Cancer Patients |
| title_sort | landscape of the peripheral immune response induced by intraoperative radiotherapy combined with surgery in early breast cancer patients |
| topic | breast cancer intraoperative radiotherapy peripheral immune response single‐cell RNA sequencing single‐cell T cell receptor sequencing |
| url | https://doi.org/10.1002/advs.202308174 |
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