Poor clinical outcomes and immunoevasive contexture in CD161+CD8+ T cells barren human pancreatic cancer
Background The role of CD161 expression on CD8+ T cells in tumor immunology has been explored in a few studies, and the clinical significance of CD161+CD8+ T cells in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study seeks to clarify the prognostic value and molecular characteristi...
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| Language: | English |
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BMJ Publishing Group
2024-03-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/3/e008694.full |
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| author | Jun Yu Liang Liu Hanlin Yin Qiangda Chen Siyao Liu Wenchuan Wu Ning Pu Wenhui Lou Zhenlai Jiang Taochen He Yuqi Xie Weilin Mao Jiande Han Joseph R Habib |
| author_facet | Jun Yu Liang Liu Hanlin Yin Qiangda Chen Siyao Liu Wenchuan Wu Ning Pu Wenhui Lou Zhenlai Jiang Taochen He Yuqi Xie Weilin Mao Jiande Han Joseph R Habib |
| author_sort | Jun Yu |
| collection | DOAJ |
| description | Background The role of CD161 expression on CD8+ T cells in tumor immunology has been explored in a few studies, and the clinical significance of CD161+CD8+ T cells in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study seeks to clarify the prognostic value and molecular characteristics linked to CD161+CD8+ T cell infiltration in PDAC.Methods This study included 186 patients with confirmed PDAC histology after radical resection. CD161+CD8+ T cell infiltration was assessed using immunofluorescence staining on tumor microarrays. Flow cytometry and single-cell RNA sequencing were used to evaluate their functional status.Results We observed significant associations between tumor-infiltrating CD161+CD8+ T cells and clinicopathological factors, such as tumor differentiation, perineural invasion, and serum CA19-9 levels. Patients with higher tumor-infiltrating CD161+CD8+ T cell levels had longer overall survival (OS) and recurrence-free survival (RFS) than those with lower levels. Multivariable analysis confirmed tumor-infiltrating CD161+CD8+ T cell as an independent prognostic indicator for both OS and RFS. Notably, a combination of tumor-infiltrating CD161+CD8+ T cell and CA19-9 levels showed a superior power for survival prediction, and patients with low tumor-infiltrating CD161+CD8+ T cell and high CA19-9 levels had the worst survival. Furthermore, lower tumor-infiltrating CD161+CD8+ T cells were associated with a better response to adjuvant chemotherapy. Finally, we identified tumor-infiltrating CD161+CD8+ T cells as a unique subtype of responsive CD8+ T cells characterized by increased levels of cytotoxic cytokines and immune checkpoint molecules.Conclusion CD161+CD8+ T cells exhibit elevated levels of both cytotoxic and immune-checkpoint molecules, indicating as a potential and attractive target for immunotherapy. The tumor-infiltrating CD161+CD8+ T cell is a valuable and promising predictor for survival and therapeutic response to adjuvant chemotherapy in PDAC. Further research is warranted to validate its role in the risk stratification and optimization of therapeutic strategies. |
| format | Article |
| id | doaj-art-3f67934b5e2a4cf88c4adf5e5cf6f918 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2024-03-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-3f67934b5e2a4cf88c4adf5e5cf6f9182024-12-18T01:40:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-03-0112310.1136/jitc-2023-008694Poor clinical outcomes and immunoevasive contexture in CD161+CD8+ T cells barren human pancreatic cancerJun Yu0Liang Liu1Hanlin Yin2Qiangda Chen3Siyao Liu4Wenchuan Wu5Ning Pu6Wenhui Lou7Zhenlai Jiang8Taochen He9Yuqi Xie10Weilin Mao11Jiande Han12Joseph R Habib13Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong SAR, China10 State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, Chinajunior physicianDepartment of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China2 Cancer Center, Zhongshan Hospital Fudan University, Shanghai, ChinaDepartment of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China2 Cancer Center, Zhongshan Hospital Fudan University, Shanghai, China1 Department of Pancreatic Surgery, Zhongshan Hospital Fudan University, Shanghai, China1 Department of Pancreatic Surgery, Zhongshan Hospital Fudan University, Shanghai, China1 Department of Pancreatic Surgery, Zhongshan Hospital Fudan University, Shanghai, China1 Department of Pancreatic Surgery, Zhongshan Hospital Fudan University, Shanghai, China1 Department of Pancreatic Surgery, Zhongshan Hospital Fudan University, Shanghai, China3 Department of Surgery, New York University School of Medicine and NYU Langone Medical Center, New York, New York, USABackground The role of CD161 expression on CD8+ T cells in tumor immunology has been explored in a few studies, and the clinical significance of CD161+CD8+ T cells in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study seeks to clarify the prognostic value and molecular characteristics linked to CD161+CD8+ T cell infiltration in PDAC.Methods This study included 186 patients with confirmed PDAC histology after radical resection. CD161+CD8+ T cell infiltration was assessed using immunofluorescence staining on tumor microarrays. Flow cytometry and single-cell RNA sequencing were used to evaluate their functional status.Results We observed significant associations between tumor-infiltrating CD161+CD8+ T cells and clinicopathological factors, such as tumor differentiation, perineural invasion, and serum CA19-9 levels. Patients with higher tumor-infiltrating CD161+CD8+ T cell levels had longer overall survival (OS) and recurrence-free survival (RFS) than those with lower levels. Multivariable analysis confirmed tumor-infiltrating CD161+CD8+ T cell as an independent prognostic indicator for both OS and RFS. Notably, a combination of tumor-infiltrating CD161+CD8+ T cell and CA19-9 levels showed a superior power for survival prediction, and patients with low tumor-infiltrating CD161+CD8+ T cell and high CA19-9 levels had the worst survival. Furthermore, lower tumor-infiltrating CD161+CD8+ T cells were associated with a better response to adjuvant chemotherapy. Finally, we identified tumor-infiltrating CD161+CD8+ T cells as a unique subtype of responsive CD8+ T cells characterized by increased levels of cytotoxic cytokines and immune checkpoint molecules.Conclusion CD161+CD8+ T cells exhibit elevated levels of both cytotoxic and immune-checkpoint molecules, indicating as a potential and attractive target for immunotherapy. The tumor-infiltrating CD161+CD8+ T cell is a valuable and promising predictor for survival and therapeutic response to adjuvant chemotherapy in PDAC. Further research is warranted to validate its role in the risk stratification and optimization of therapeutic strategies.https://jitc.bmj.com/content/12/3/e008694.full |
| spellingShingle | Jun Yu Liang Liu Hanlin Yin Qiangda Chen Siyao Liu Wenchuan Wu Ning Pu Wenhui Lou Zhenlai Jiang Taochen He Yuqi Xie Weilin Mao Jiande Han Joseph R Habib Poor clinical outcomes and immunoevasive contexture in CD161+CD8+ T cells barren human pancreatic cancer Journal for ImmunoTherapy of Cancer |
| title | Poor clinical outcomes and immunoevasive contexture in CD161+CD8+ T cells barren human pancreatic cancer |
| title_full | Poor clinical outcomes and immunoevasive contexture in CD161+CD8+ T cells barren human pancreatic cancer |
| title_fullStr | Poor clinical outcomes and immunoevasive contexture in CD161+CD8+ T cells barren human pancreatic cancer |
| title_full_unstemmed | Poor clinical outcomes and immunoevasive contexture in CD161+CD8+ T cells barren human pancreatic cancer |
| title_short | Poor clinical outcomes and immunoevasive contexture in CD161+CD8+ T cells barren human pancreatic cancer |
| title_sort | poor clinical outcomes and immunoevasive contexture in cd161 cd8 t cells barren human pancreatic cancer |
| url | https://jitc.bmj.com/content/12/3/e008694.full |
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