IFN gamma enhances cytotoxic efficiency of the cytotoxic T lymphocytes against human glioma cells

摘要

Cytotoxic T lymphocytes (CTLs) are a key player in cancer immunotherapies, and MHC class I molecules on the cell surface are crucial for cellular recognition. However, the aberrant expression of MHC class I molecules is frequently found in various malignancies. IFN gamma has dual functions in cancer progression, and its effect on tumor immunity is controversial. To investigate whether IFN gamma can enhance cytotoxic efficiency of the tumor antigen specific CTLs, we generated the CTLs using modified human dendritic cells as antigen presenting cells, then studied the activities of CTLs on human leukocyte antigen (HLA)-A2 positive glioma cells treated with, or without IFN gamma. The results from both ELISpot and cytotoxicity assays demonstrated that the CTLs recognized and eliminated the HLA-A2 positive glioma cells treated with IFN gamma more effectively when compared to the glioma cells deprived of IFN gamma treatment. In addition, in vitro experiments showed that the levels of MHC class I molecules were upregulated in all of the HLA-A2 positive glioma cells. Using the publicly accessed TCGA data of low-grade glioma, we found significantly positive associations between IFN gamma and both MHC class I molecules and CD8(+) T cell activation score (p < 0.0001). Furthermore, we found a significantly reduced risk of death in the glioma patients with high T cell activation score in comparison to those with low score (p = 0.022). These findings suggest that a clinical application of IFN gamma treatment may have potential benefits.