Hui Zheng, Xiaolin Guan, Xin Meng, Ying Tong, Yanchun Wang, Suhong Xie, Lin Guo, Renquan Lu
Journal of ovarian research 2023 Nov 25Inflammation 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. 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. 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. 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. © 2023. The Author(s).
Hui Zheng, Xiaolin Guan, Xin Meng, Ying Tong, Yanchun Wang, Suhong Xie, Lin Guo, Renquan Lu. IFN-γ in ovarian tumor microenvironment upregulates HLA-E expression and predicts a poor prognosis. Journal of ovarian research. 2023 Nov 25;16(1):229
PMID: 38007483
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