Hypoxia inhibits the iMo/cDC2/CD8+ TRMs immune axis in the tumor microenvironment of human esophageal cancer
Background Esophageal cancer (ESCA) is a form of malignant tumor associated with chronic inflammation and immune dysregulation. However, the specific immune status and key mechanisms of immune regulation in this disease require further exploration.Methods To investigate the features of the human ESC...
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BMJ Publishing Group
2024-07-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/7/e008889.full |
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| author | Qi Wang Bin Jiang Ming Wu Ming Chen Fuxiang Liang Hong Shen Pin Wu Yafei Liu Chuanqiang Wu Huan Yu Xiancong Huang Zhiling Lou Zixiang Wu |
| author_facet | Qi Wang Bin Jiang Ming Wu Ming Chen Fuxiang Liang Hong Shen Pin Wu Yafei Liu Chuanqiang Wu Huan Yu Xiancong Huang Zhiling Lou Zixiang Wu |
| author_sort | Qi Wang |
| collection | DOAJ |
| description | Background Esophageal cancer (ESCA) is a form of malignant tumor associated with chronic inflammation and immune dysregulation. However, the specific immune status and key mechanisms of immune regulation in this disease require further exploration.Methods To investigate the features of the human ESCA tumor immune microenvironment and its possible regulation, we performed mass cytometry by time of flight, single-cell RNA sequencing, multicolor fluorescence staining of tissue, and flow cytometry analyses on tumor and paracancerous tissue from treatment-naïve patients.Results We depicted the immune landscape of the ESCA and revealed that CD8+ (tissue-resident memory CD8+ T cells (CD8+ TRMs) were closely related to disease progression. We also revealed the heterogeneity of CD8+ TRMs in the ESCA tumor microenvironment (TME), which was associated with their differentiation and function. Moreover, the subset of CD8+ TRMs in tumor (called tTRMs) that expressed high levels of granzyme B and immune checkpoints was markedly decreased in the TME of advanced ESCA. We showed that tTRMs are tumor effector cells preactivated in the TME. We then demonstrated that conventional dendritic cells (cDC2s) derived from intermediate monocytes (iMos) are essential for maintaining the proliferation of CD8+ TRMs in the TME. Our preliminary study showed that hypoxia can promote the apoptosis of iMos and impede the maturation of cDC2s, which in turn reduces the proliferative capacity of CD8+ TRMs, thereby contributing to the progression of cancer.Conclusions Our study revealed the essential antitumor roles of CD8+ TRMs and preliminarily explored the regulation of the iMo/cDC2/CD8+ TRM immune axis in the human ESCA TME. |
| format | Article |
| id | doaj-art-db88ee00577d43e0a3f437ba16403b3b |
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| issn | 2051-1426 |
| language | English |
| publishDate | 2024-07-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-db88ee00577d43e0a3f437ba16403b3b2025-08-20T02:02:20ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-07-0112710.1136/jitc-2024-008889Hypoxia inhibits the iMo/cDC2/CD8+ TRMs immune axis in the tumor microenvironment of human esophageal cancerQi Wang0Bin Jiang1Ming Wu2Ming Chen3Fuxiang Liang4Hong Shen5Pin Wu6Yafei Liu7Chuanqiang Wu8Huan Yu9Xiancong Huang10Zhiling Lou11Zixiang Wu12State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, ChinaDepartment of Radiology, Stanford University, Stanford, California, USADepartment of Nursing, Fujian Health College, Fuzhou, China1 Department of Dermatology, The First Affiliated Hospital of Jinan University and Jinan University Institute of Dermatology, Guangzhou, China1 Department of Thoracic Surgery, The Second Affiliated Hospital Zhejiang University School of Medicine,Zhejiang University, Hangzhou, Zhejiang Province, People`s Republic of China5 Department of Medical Oncology, The Second Affiliated Hospital Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People`s Republic of ChinaDepartment of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China1 Department of Thoracic Surgery, The Second Affiliated Hospital Zhejiang University School of Medicine,Zhejiang University, Hangzhou, Zhejiang Province, People`s Republic of China1 Department of Thoracic Surgery, The Second Affiliated Hospital Zhejiang University School of Medicine,Zhejiang University, Hangzhou, Zhejiang Province, People`s Republic of China1 Department of Thoracic Surgery, The Second Affiliated Hospital Zhejiang University School of Medicine,Zhejiang University, Hangzhou, Zhejiang Province, People`s Republic of China1 Department of Thoracic Surgery, The Second Affiliated Hospital Zhejiang University School of Medicine,Zhejiang University, Hangzhou, Zhejiang Province, People`s Republic of China1 Department of Thoracic Surgery, The Second Affiliated Hospital Zhejiang University School of Medicine,Zhejiang University, Hangzhou, Zhejiang Province, People`s Republic of China1 Department of Thoracic Surgery, The Second Affiliated Hospital Zhejiang University School of Medicine,Zhejiang University, Hangzhou, Zhejiang Province, People`s Republic of ChinaBackground Esophageal cancer (ESCA) is a form of malignant tumor associated with chronic inflammation and immune dysregulation. However, the specific immune status and key mechanisms of immune regulation in this disease require further exploration.Methods To investigate the features of the human ESCA tumor immune microenvironment and its possible regulation, we performed mass cytometry by time of flight, single-cell RNA sequencing, multicolor fluorescence staining of tissue, and flow cytometry analyses on tumor and paracancerous tissue from treatment-naïve patients.Results We depicted the immune landscape of the ESCA and revealed that CD8+ (tissue-resident memory CD8+ T cells (CD8+ TRMs) were closely related to disease progression. We also revealed the heterogeneity of CD8+ TRMs in the ESCA tumor microenvironment (TME), which was associated with their differentiation and function. Moreover, the subset of CD8+ TRMs in tumor (called tTRMs) that expressed high levels of granzyme B and immune checkpoints was markedly decreased in the TME of advanced ESCA. We showed that tTRMs are tumor effector cells preactivated in the TME. We then demonstrated that conventional dendritic cells (cDC2s) derived from intermediate monocytes (iMos) are essential for maintaining the proliferation of CD8+ TRMs in the TME. Our preliminary study showed that hypoxia can promote the apoptosis of iMos and impede the maturation of cDC2s, which in turn reduces the proliferative capacity of CD8+ TRMs, thereby contributing to the progression of cancer.Conclusions Our study revealed the essential antitumor roles of CD8+ TRMs and preliminarily explored the regulation of the iMo/cDC2/CD8+ TRM immune axis in the human ESCA TME.https://jitc.bmj.com/content/12/7/e008889.full |
| spellingShingle | Qi Wang Bin Jiang Ming Wu Ming Chen Fuxiang Liang Hong Shen Pin Wu Yafei Liu Chuanqiang Wu Huan Yu Xiancong Huang Zhiling Lou Zixiang Wu Hypoxia inhibits the iMo/cDC2/CD8+ TRMs immune axis in the tumor microenvironment of human esophageal cancer Journal for ImmunoTherapy of Cancer |
| title | Hypoxia inhibits the iMo/cDC2/CD8+ TRMs immune axis in the tumor microenvironment of human esophageal cancer |
| title_full | Hypoxia inhibits the iMo/cDC2/CD8+ TRMs immune axis in the tumor microenvironment of human esophageal cancer |
| title_fullStr | Hypoxia inhibits the iMo/cDC2/CD8+ TRMs immune axis in the tumor microenvironment of human esophageal cancer |
| title_full_unstemmed | Hypoxia inhibits the iMo/cDC2/CD8+ TRMs immune axis in the tumor microenvironment of human esophageal cancer |
| title_short | Hypoxia inhibits the iMo/cDC2/CD8+ TRMs immune axis in the tumor microenvironment of human esophageal cancer |
| title_sort | hypoxia inhibits the imo cdc2 cd8 trms immune axis in the tumor microenvironment of human esophageal cancer |
| url | https://jitc.bmj.com/content/12/7/e008889.full |
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