| Autor: |
Hui Zheng, Xiaolin Guan, Xin Meng, Ying Tong, Yanchun Wang, Suhong Xie, Lin Guo, Renquan Lu |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Journal of Ovarian Research, Vol 16, Iss 1, Pp 1-9 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1757-2215 |
| DOI: |
10.1186/s13048-023-01286-z |
| Popis: |
Abstract Background Inflammation and immunity are two main characteristics of tumor microenvironment (TME). Interferon-gamma (IFN-γ) is generally considered as a pro-inflammatory cytokine which mediates anti-tumor immune response. Recently, IFN-γ was also reported to play a protumorigenic role. However, the mechanisms of tumor-promoting effect induced by IFN-γ remain unclear. Methods The expression of leukocyte antigen-E (HLA-E), IFN-γ, CD3 and CD56 in clinical samples of ovarian cancer was detected by mutiplexed immunohistochemistry. The mechanism to induce HLA-E overexpression by IFN-γ was explored using human ovarian cancer cell lines through western blot and flow cytometry. We further clarify the role of overexpressed-HLA-E on natural killer (NK)-mediated cell lysis. Results We found that IFN-γ could upregulate HLA-E protein expression through activating of JAK/STAT1 signaling pathway, and increase cell surface HLA-E level through enhancing proteasome activity. We also observed that only high levels of membrane HLA-E expression contributed to the inhibition of NK-mediated cytotoxicity. We showed that progression-free survival (PFS) of ovarian cancer patients was negatively correlated with IFN-γ expression in their tumor tissues, due to more tumor infiltrating NK cells compared with T lymphocytes. Conclusions Our study revealed the protumorigenic role of IFN-γ by upregulation of HLA-E expression and rendering tumors less susceptible to immune attack. We also provided a novel insight into the relationship between tumor microenvironment and immune evasion. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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