Clinicopathological and predictive value of MAIT cells in non-small cell lung cancer for immunotherapy
Background Immune-checkpoint inhibitors (ICIs) remain ineffective in a large group of non-small cell lung cancer (NSCLC) patients. Mucosal-associated invariant T (MAIT) cells, a population of unconventional innate-like T lymphocytes abundant in the human body, play important roles in human malignanc...
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BMJ Publishing Group
2023-01-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/11/1/e005902.full |
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| author | Dongyan Shi Lin Lin Yun Chen Jian Liu Lin Shi Jinying Lu Da Zhong Meijuan Song Wenhua You Wen-Hui Li |
| author_facet | Dongyan Shi Lin Lin Yun Chen Jian Liu Lin Shi Jinying Lu Da Zhong Meijuan Song Wenhua You Wen-Hui Li |
| author_sort | Dongyan Shi |
| collection | DOAJ |
| description | Background Immune-checkpoint inhibitors (ICIs) remain ineffective in a large group of non-small cell lung cancer (NSCLC) patients. Mucosal-associated invariant T (MAIT) cells, a population of unconventional innate-like T lymphocytes abundant in the human body, play important roles in human malignancies. Little is known about the immune characteristics of MAIT cells in NSCLC and correlation with prognosis and response rate of ICIs treatment.Methods To investigate the distribution, activation status, and function of MAIT cells in NSCLC patients and their correlations with anti-PD-1 immunotherapy, MAIT cells in peripheral blood, tumor and paratumor samples from NSCLC patients with or without anti-PD-1 immunotherapy were analyzed using flow cytometry and single-cell RNA-sequencing.Results MAIT cells were enriched in the tumor lesions of NSCLC patients migrating from peripheral blood via the CCR6-CCL20 axis. Both peripheral and tumor-infiltrating MAIT cells displayed an exhausted phenotype with upregulated PD-1, TIM-3, and IL-17A while less IFN-γ. Anti-PD-1 therapy reversed the function of circulating MAIT cells with higher expression of IFN-γ and granzyme B. Subcluster MAIT-17s (defined as cells highly expressing exhausted and Th17-related genes) mainly infiltrated in the non-responsive tissues, while the subcluster MAIT-IFNGRs (cells expressing genes related to cytotoxic function) were mainly enriched in responsive tissues. Moreover, we found predictive value of circulating MAIT cells for anti-PD-1 immunotherapy in NSCLC patients.Conclusions MAIT cells shifted to an exhausted tumor-promoting phenotype in NSCLC patients and the circulating MAIT subset could be a predictor for patients who respond to anti-PD-1 immunotherapy. |
| format | Article |
| id | doaj-art-586028287e1c4f36a74e23ad8774748c |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-586028287e1c4f36a74e23ad8774748c2025-01-29T09:35:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262023-01-0111110.1136/jitc-2022-005902Clinicopathological and predictive value of MAIT cells in non-small cell lung cancer for immunotherapyDongyan Shi0Lin Lin1Yun Chen2Jian Liu3Lin Shi4Jinying Lu5Da Zhong6Meijuan Song7Wenhua You8Wen-Hui Li9Department of Immunology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Gusu School, Nanjing Medical University, Nanjing, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China1 Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Rheumatology and Immunology, Sichuan Provincial People`s Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Immunology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Gusu School, Nanjing Medical University, Nanjing, ChinaThe Affiliated Wuxi People`s Hospital of Nanjing Medical University, Wuxi People`s Hospital, Wuxi Medical Center & Department of Immunology, School of Basic Medical Sciences, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, ChinaDepartment of Immunology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Gusu School, Nanjing Medical University, Nanjing, ChinaDepartment of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaSchool of Chemistry and Chemical Engineering, Center of Interventional Radiology and Vascular Surgery, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu, ChinaDepartment of Hepatobiliary Surgery, The Yancheng School of Clinical Medicine of Nanjing Medical University, The Third People’s Hospital of Yancheng, Yancheng, ChinaBackground Immune-checkpoint inhibitors (ICIs) remain ineffective in a large group of non-small cell lung cancer (NSCLC) patients. Mucosal-associated invariant T (MAIT) cells, a population of unconventional innate-like T lymphocytes abundant in the human body, play important roles in human malignancies. Little is known about the immune characteristics of MAIT cells in NSCLC and correlation with prognosis and response rate of ICIs treatment.Methods To investigate the distribution, activation status, and function of MAIT cells in NSCLC patients and their correlations with anti-PD-1 immunotherapy, MAIT cells in peripheral blood, tumor and paratumor samples from NSCLC patients with or without anti-PD-1 immunotherapy were analyzed using flow cytometry and single-cell RNA-sequencing.Results MAIT cells were enriched in the tumor lesions of NSCLC patients migrating from peripheral blood via the CCR6-CCL20 axis. Both peripheral and tumor-infiltrating MAIT cells displayed an exhausted phenotype with upregulated PD-1, TIM-3, and IL-17A while less IFN-γ. Anti-PD-1 therapy reversed the function of circulating MAIT cells with higher expression of IFN-γ and granzyme B. Subcluster MAIT-17s (defined as cells highly expressing exhausted and Th17-related genes) mainly infiltrated in the non-responsive tissues, while the subcluster MAIT-IFNGRs (cells expressing genes related to cytotoxic function) were mainly enriched in responsive tissues. Moreover, we found predictive value of circulating MAIT cells for anti-PD-1 immunotherapy in NSCLC patients.Conclusions MAIT cells shifted to an exhausted tumor-promoting phenotype in NSCLC patients and the circulating MAIT subset could be a predictor for patients who respond to anti-PD-1 immunotherapy.https://jitc.bmj.com/content/11/1/e005902.full |
| spellingShingle | Dongyan Shi Lin Lin Yun Chen Jian Liu Lin Shi Jinying Lu Da Zhong Meijuan Song Wenhua You Wen-Hui Li Clinicopathological and predictive value of MAIT cells in non-small cell lung cancer for immunotherapy Journal for ImmunoTherapy of Cancer |
| title | Clinicopathological and predictive value of MAIT cells in non-small cell lung cancer for immunotherapy |
| title_full | Clinicopathological and predictive value of MAIT cells in non-small cell lung cancer for immunotherapy |
| title_fullStr | Clinicopathological and predictive value of MAIT cells in non-small cell lung cancer for immunotherapy |
| title_full_unstemmed | Clinicopathological and predictive value of MAIT cells in non-small cell lung cancer for immunotherapy |
| title_short | Clinicopathological and predictive value of MAIT cells in non-small cell lung cancer for immunotherapy |
| title_sort | clinicopathological and predictive value of mait cells in non small cell lung cancer for immunotherapy |
| url | https://jitc.bmj.com/content/11/1/e005902.full |
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