Dataset Information

IFN-γ in ovarian tumor microenvironment upregulates HLA-E expression and predicts a poor prognosis.

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.

SUBMITTER: Zheng H

PROVIDER: S-EPMC10675946 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

IFN-γ in ovarian tumor microenvironment upregulates HLA-E expression and predicts a poor prognosis.

Zheng Hui H Guan Xiaolin X Meng Xin X Tong Ying Y Wang Yanchun Y Xie Suhong S Guo Lin L Lu Renquan R

Journal of ovarian research 20231125 1

<h4>Background</h4>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.<h4>Methods</h4>The expression of leukocyte antigen-E (HLA-E), IFN-γ, CD3 and CD56 in clinical samples of ovarian cancer wa ...[more]

PMID: 38007483

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Dataset Information

IFN-γ in ovarian tumor microenvironment upregulates HLA-E expression and predicts a poor prognosis.

Background

Methods

Results

Conclusions

Publications

IFN-γ in ovarian tumor microenvironment upregulates HLA-E expression and predicts a poor prognosis.

Similar Datasets

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