Multiomics profiling reveals the benefits of gamma-delta (γδ) T lymphocytes for improving the tumor microenvironment, immunotherapy efficacy and prognosis in cervical cancer
Background As an unconventional subpopulation of T lymphocytes, γδ T cells can recognize antigens independently of major histocompatibility complex restrictions. Recent studies have indicated that γδ T cells play contrasting roles in tumor microenvironments—promoting tumor progression in some cancer...
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| Language: | English |
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BMJ Publishing Group
2024-01-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/1/e008355.full |
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| author | Xiaofeng Wang Chen Li Jie Chen Zhiqiang Wu Zhen Zhang Junyi Li Lu Yu Yong Guan Yuhan Zhang Yuanjie Cao Yancheng Liu Hui Bai Shaochuan Liu Miaomiao Gao Chenglu Lu Zhen Tao Zhiyong Yuan |
| author_facet | Xiaofeng Wang Chen Li Jie Chen Zhiqiang Wu Zhen Zhang Junyi Li Lu Yu Yong Guan Yuhan Zhang Yuanjie Cao Yancheng Liu Hui Bai Shaochuan Liu Miaomiao Gao Chenglu Lu Zhen Tao Zhiyong Yuan |
| author_sort | Xiaofeng Wang |
| collection | DOAJ |
| description | Background As an unconventional subpopulation of T lymphocytes, γδ T cells can recognize antigens independently of major histocompatibility complex restrictions. Recent studies have indicated that γδ T cells play contrasting roles in tumor microenvironments—promoting tumor progression in some cancers (eg, gallbladder and leukemia) while suppressing it in others (eg, lung and gastric). γδ T cells are mainly enriched in peripheral mucosal tissues. As the cervix is a mucosa-rich tissue, the role of γδ T cells in cervical cancer warrants further investigation.Methods We employed a multiomics strategy that integrated abundant data from single-cell and bulk transcriptome sequencing, whole exome sequencing, genotyping array, immunohistochemistry, and MRI.Results Heterogeneity was observed in the level of γδ T-cell infiltration in cervical cancer tissues, mainly associated with the tumor somatic mutational landscape. Definitely, γδ T cells play a beneficial role in the prognosis of patients with cervical cancer. First, γδ T cells exert direct cytotoxic effects in the tumor microenvironment of cervical cancer through the dynamic evolution of cellular states at both poles. Second, higher levels of γδ T-cell infiltration also shape the microenvironment of immune activation with cancer-suppressive properties. We found that these intricate features can be observed by MRI-based radiomics models to non-invasively assess γδ T-cell proportions in tumor tissues in patients. Importantly, patients with high infiltration levels of γδ T cells may be more amenable to immunotherapies including immune checkpoint inhibitors and autologous tumor-infiltrating lymphocyte therapies, than to chemoradiotherapy.Conclusions γδ T cells play a beneficial role in antitumor immunity in cervical cancer. The abundance of γδ T cells in cervical cancerous tissue is associated with higher response rates to immunotherapy. |
| format | Article |
| id | doaj-art-fc82d0ec90a245cd9013c965b5115511 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-fc82d0ec90a245cd9013c965b51155112025-02-03T16:05:14ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-01-0112110.1136/jitc-2023-008355Multiomics profiling reveals the benefits of gamma-delta (γδ) T lymphocytes for improving the tumor microenvironment, immunotherapy efficacy and prognosis in cervical cancerXiaofeng Wang0Chen Li1Jie Chen2Zhiqiang Wu3Zhen Zhang4Junyi Li5Lu Yu6Yong Guan7Yuhan Zhang8Yuanjie Cao9Yancheng Liu10Hui Bai11Shaochuan Liu12Miaomiao Gao13Chenglu Lu14Zhen Tao15Zhiyong Yuan162 Human Phenome Institute, Fudan University, Shanghai, ChinaPeking University People’s Hospital, Beijing, ChinaprofessorDepartment of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin`s Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin, China3Moderna, Inc., Cambridge, MA, USA1 Department of Cell Biology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, ChinaDepartment of Neurology, Xiamen Susong Hospital, Xiamen, ChinaThe First Clinical Medical College of Lanzhou University, Lanzhou, Gansu, ChinaNational Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute & Hospital, Tianjin, ChinaDepartment of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin`s Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin`s Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin`s Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin`s Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin`s Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Pathology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, ChinaDepartment of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin`s Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin, ChinaDepartment of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin`s Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin, ChinaBackground As an unconventional subpopulation of T lymphocytes, γδ T cells can recognize antigens independently of major histocompatibility complex restrictions. Recent studies have indicated that γδ T cells play contrasting roles in tumor microenvironments—promoting tumor progression in some cancers (eg, gallbladder and leukemia) while suppressing it in others (eg, lung and gastric). γδ T cells are mainly enriched in peripheral mucosal tissues. As the cervix is a mucosa-rich tissue, the role of γδ T cells in cervical cancer warrants further investigation.Methods We employed a multiomics strategy that integrated abundant data from single-cell and bulk transcriptome sequencing, whole exome sequencing, genotyping array, immunohistochemistry, and MRI.Results Heterogeneity was observed in the level of γδ T-cell infiltration in cervical cancer tissues, mainly associated with the tumor somatic mutational landscape. Definitely, γδ T cells play a beneficial role in the prognosis of patients with cervical cancer. First, γδ T cells exert direct cytotoxic effects in the tumor microenvironment of cervical cancer through the dynamic evolution of cellular states at both poles. Second, higher levels of γδ T-cell infiltration also shape the microenvironment of immune activation with cancer-suppressive properties. We found that these intricate features can be observed by MRI-based radiomics models to non-invasively assess γδ T-cell proportions in tumor tissues in patients. Importantly, patients with high infiltration levels of γδ T cells may be more amenable to immunotherapies including immune checkpoint inhibitors and autologous tumor-infiltrating lymphocyte therapies, than to chemoradiotherapy.Conclusions γδ T cells play a beneficial role in antitumor immunity in cervical cancer. The abundance of γδ T cells in cervical cancerous tissue is associated with higher response rates to immunotherapy.https://jitc.bmj.com/content/12/1/e008355.full |
| spellingShingle | Xiaofeng Wang Chen Li Jie Chen Zhiqiang Wu Zhen Zhang Junyi Li Lu Yu Yong Guan Yuhan Zhang Yuanjie Cao Yancheng Liu Hui Bai Shaochuan Liu Miaomiao Gao Chenglu Lu Zhen Tao Zhiyong Yuan Multiomics profiling reveals the benefits of gamma-delta (γδ) T lymphocytes for improving the tumor microenvironment, immunotherapy efficacy and prognosis in cervical cancer Journal for ImmunoTherapy of Cancer |
| title | Multiomics profiling reveals the benefits of gamma-delta (γδ) T lymphocytes for improving the tumor microenvironment, immunotherapy efficacy and prognosis in cervical cancer |
| title_full | Multiomics profiling reveals the benefits of gamma-delta (γδ) T lymphocytes for improving the tumor microenvironment, immunotherapy efficacy and prognosis in cervical cancer |
| title_fullStr | Multiomics profiling reveals the benefits of gamma-delta (γδ) T lymphocytes for improving the tumor microenvironment, immunotherapy efficacy and prognosis in cervical cancer |
| title_full_unstemmed | Multiomics profiling reveals the benefits of gamma-delta (γδ) T lymphocytes for improving the tumor microenvironment, immunotherapy efficacy and prognosis in cervical cancer |
| title_short | Multiomics profiling reveals the benefits of gamma-delta (γδ) T lymphocytes for improving the tumor microenvironment, immunotherapy efficacy and prognosis in cervical cancer |
| title_sort | multiomics profiling reveals the benefits of gamma delta γδ t lymphocytes for improving the tumor microenvironment immunotherapy efficacy and prognosis in cervical cancer |
| url | https://jitc.bmj.com/content/12/1/e008355.full |
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