| Autor: |
Bing Huang, Peiliang Wang, Zhiwei Yuan, Jianjian Yang, Hui Xiong, Ni Zhang, Qi Huang, Xiangning Fu |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
Journal for ImmunoTherapy of Cancer, Vol 8, Iss 1 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2051-1426 |
| DOI: |
10.1136/jitc-2020-000639 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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