Acidic environment could modulate the interferon-γ expression: Implication on modulation of cancer and immune cells’ interactions
Article Category: Original article
Published Online: Sep 17, 2023
Page range: 72 - 83
DOI: https://doi.org/10.2478/abm-2023-0047
Keywords
© 2023 Vishal Sharma et al., published by Sciendo
This work is licensed under the Creative Commons Attribution 4.0 International License.
Background
In rapidly growing solid tumors, insufficient vascularization and poor oxygen supply result in an acidic tumor microenvironment, which can alter immune response.
Objective
To investigate the role of the acidic microenvironment in immune response modulation along with cancer and immune cells’ interactions.
Method
To mimic the tumor microenvironment conditions, T cells (Jurkat), macrophages (THP-1), and HeLa (cervical) cells were cultured under acidic conditions (pH 6.9, pH 6.5) and physiological pH (7.4). The HeLa cell culture medium was exploited as a tumor cell conditioned medium. Real-time PCR was carried out to quantify the mRNA levels, while flow cytometry and western blot hybridization was carried out to ascertain the levels of different proteins.
Results
The acidic microenvironment around the T cells (Jurkat) and macrophage cells (THP-1) could lead to the downregulation of the interferon gamma (IFN-γ). An increase in IFN-γ expression was observed when Jurkat and macrophage cells were cultured in HeLa cells conditioned medium (HCM) at low pH (pH 6.9, pH 6.5). The HeLa cells under acidic environment (pH 6.9, pH 6.5) upregulated interleukin 18 levels and secreted it as exosome anchored. Additionally, enhanced nuclear localization of NF-κB was observed in Jurkat and THP-1 cells cultured in HCM (pH 6.9, pH 6.5). Jurkat and THP-1 cultured in HCM revealed enhanced cytotoxicity against the HeLa cells upon reverting the pH of the medium from acidic to physiological pH (pH 7.4).
Conclusion
Collectively, these results suggest that the acidic microenvironment acted as a key barrier to cancer and immune cells’ interactions.