CD8+CD57+ T cells exhibit distinct features in human non-small cell lung cancer
Background The repetitive antigen stimulation during chronic infection often leads to the accumulation of CD8+CD57+ T cells. These cells express high levels of interferon-γ, granzyme B and perforin with elevated cytolytic effect, and are considered as the most potent cells for combating chronical vi...
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| Format: | Article |
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BMJ Publishing Group
2020-05-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/1/e000639.full |
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| author | Wei Sun Rong Liu Bing Huang Peiliang Wang Zhiwei Yuan Jianjian Yang Hui Xiong Ni Zhang Qi Huang Xiangning Fu Lequn Li |
| author_facet | Wei Sun Rong Liu Bing Huang Peiliang Wang Zhiwei Yuan Jianjian Yang Hui Xiong Ni Zhang Qi Huang Xiangning Fu Lequn Li |
| author_sort | Wei Sun |
| collection | DOAJ |
| description | Background The repetitive antigen stimulation during chronic infection often leads to the accumulation of CD8+CD57+ T cells. These cells express high levels of interferon-γ, granzyme B and perforin with elevated cytolytic effect, and are considered as the most potent cells for combating chronical viral infection. The status of CD8+CD57+ T cells in non-small cell lung cancer (NSCLC) has not been well defined.Methods We used flow cytometry and undertook a systemic approach to examine the frequency, immunophenotyping and functional properties of CD8+CD57+ T cells in the peripheral blood, tumor tissue and the corresponding normal tissue, as well as lung draining lymph nodes, of patients with NSCLC.Results CD57+ T cells expressed high levels of programmed cell death-1 (PD-1) in all tested compartments and were predominantly CD8+ T cells. These cells in the peripheral blood displayed a terminally differentiated phenotype as defined by loss of CD27 and CD28 while expressing KLRG1. CD8+CD57+ T cells exhibited enhanced cytotoxic potencies and impaired proliferative capability. Unlike CD57+ T cells in the peripheral blood, a significant proportion of CD57+ T cells in the primary tumors expressed CD27 and CD28. CD8+CD57+ T cells in tumors lacked cytotoxic activity. The proliferative activity of these cells was also impaired. CD8+CD57+ T cells in the corresponding normal lung tissues shared similarities with their counterparts in peripheral blood rather than their counterparts in tumors. The vast majority of CD8+CD57+ T cells in lung draining lymph nodes were positive for CD27 and CD28. These cells were unable to produce perforin and granzyme B, but their proliferative activity was preserved. CD8+CD57+ T cells in tumors displayed an inferior response to PD-1 blockade compared with their CD8+CD57- counterparts. Interleukin (IL)-15 preferentially restored the effector function of these cells. Additionally, IL-15 was able to restore the impaired proliferative activity of CD8+CD57+ T cells in tumors and peripheral blood.Conclusions Our data indicate that the failure of the immune system to fight cancer progression could be a result of impaired CD8+ T-cell functional maturation into fully differentiated effector T cells within the tumor microenvironment. Boosting IL-15 activity might promote tumor-reactive CD8+ T-cell functional maturation while preserving their proliferative activity. |
| format | Article |
| id | doaj-art-8191e0e504664e3191e45f76fd2a0697 |
| institution | DOAJ |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-8191e0e504664e3191e45f76fd2a06972025-08-20T02:49:52ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-05-018110.1136/jitc-2020-000639CD8+CD57+ T cells exhibit distinct features in human non-small cell lung cancerWei Sun0Rong Liu1Bing Huang2Peiliang Wang3Zhiwei Yuan4Jianjian Yang5Hui Xiong6Ni Zhang7Qi Huang8Xiangning Fu9Lequn Li10Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, People`s Republic of ChinaBristol Myers Squibb, New York, NY, USAHarbour BiMed Co., Ltd, Shanghai, ChinaThoracic Surgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, ChinaThoracic Surgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, ChinaThoracic Surgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China1 Department of Pediatrics, Peking University First Hospital, Beijing, ChinaThoracic Surgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Clinical Laboratory, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. ChinaThoracic Surgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China4 Department of Hepatobiliary and Pancreas Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Guangxi, ChinaBackground The repetitive antigen stimulation during chronic infection often leads to the accumulation of CD8+CD57+ T cells. These cells express high levels of interferon-γ, granzyme B and perforin with elevated cytolytic effect, and are considered as the most potent cells for combating chronical viral infection. The status of CD8+CD57+ T cells in non-small cell lung cancer (NSCLC) has not been well defined.Methods We used flow cytometry and undertook a systemic approach to examine the frequency, immunophenotyping and functional properties of CD8+CD57+ T cells in the peripheral blood, tumor tissue and the corresponding normal tissue, as well as lung draining lymph nodes, of patients with NSCLC.Results CD57+ T cells expressed high levels of programmed cell death-1 (PD-1) in all tested compartments and were predominantly CD8+ T cells. These cells in the peripheral blood displayed a terminally differentiated phenotype as defined by loss of CD27 and CD28 while expressing KLRG1. CD8+CD57+ T cells exhibited enhanced cytotoxic potencies and impaired proliferative capability. Unlike CD57+ T cells in the peripheral blood, a significant proportion of CD57+ T cells in the primary tumors expressed CD27 and CD28. CD8+CD57+ T cells in tumors lacked cytotoxic activity. The proliferative activity of these cells was also impaired. CD8+CD57+ T cells in the corresponding normal lung tissues shared similarities with their counterparts in peripheral blood rather than their counterparts in tumors. The vast majority of CD8+CD57+ T cells in lung draining lymph nodes were positive for CD27 and CD28. These cells were unable to produce perforin and granzyme B, but their proliferative activity was preserved. CD8+CD57+ T cells in tumors displayed an inferior response to PD-1 blockade compared with their CD8+CD57- counterparts. Interleukin (IL)-15 preferentially restored the effector function of these cells. Additionally, IL-15 was able to restore the impaired proliferative activity of CD8+CD57+ T cells in tumors and peripheral blood.Conclusions Our data indicate that the failure of the immune system to fight cancer progression could be a result of impaired CD8+ T-cell functional maturation into fully differentiated effector T cells within the tumor microenvironment. Boosting IL-15 activity might promote tumor-reactive CD8+ T-cell functional maturation while preserving their proliferative activity.https://jitc.bmj.com/content/8/1/e000639.full |
| spellingShingle | Wei Sun Rong Liu Bing Huang Peiliang Wang Zhiwei Yuan Jianjian Yang Hui Xiong Ni Zhang Qi Huang Xiangning Fu Lequn Li CD8+CD57+ T cells exhibit distinct features in human non-small cell lung cancer Journal for ImmunoTherapy of Cancer |
| title | CD8+CD57+ T cells exhibit distinct features in human non-small cell lung cancer |
| title_full | CD8+CD57+ T cells exhibit distinct features in human non-small cell lung cancer |
| title_fullStr | CD8+CD57+ T cells exhibit distinct features in human non-small cell lung cancer |
| title_full_unstemmed | CD8+CD57+ T cells exhibit distinct features in human non-small cell lung cancer |
| title_short | CD8+CD57+ T cells exhibit distinct features in human non-small cell lung cancer |
| title_sort | cd8 cd57 t cells exhibit distinct features in human non small cell lung cancer |
| url | https://jitc.bmj.com/content/8/1/e000639.full |
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