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Int Immunopharmacol. 2017 Jun;47:159-165. doi: 10.1016/j.intimp.2017.04.003. Epub 2017 Apr 12.

IFNγ enhances cytotoxic efficiency of the cytotoxic T lymphocytes against human glioma cells.

Author information

1
Institute of Microbiology and Immunology, Huzhou University, Huzhou, Zhejiang 313000, China.
2
Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale School of Medicine, Yale Cancer Center, New Haven, CT 06520, USA.
3
Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
4
Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA; StemImmune Inc., San Diego, CA 92122, USA. Electronic address: bminev@ucsd.edu.
5
Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA; Institute for Cancer Biology and Stem Cell Research, Huzhou University, Huzhou, Zhejiang 313000, China. Electronic address: wma@ucsd.edu.

Abstract

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. IFNγ has dual functions in cancer progression, and its effect on tumor immunity is controversial. To investigate whether IFNγ 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 IFNγ. The results from both ELISpot and cytotoxicity assays demonstrated that the CTLs recognized and eliminated the HLA-A2 positive glioma cells treated with IFNγ more effectively when compared to the glioma cells deprived of IFNγ 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 IFNγ 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 IFNγ treatment may have potential benefits.

KEYWORDS:

Interferon gamma (IFNγ); Poly (lactide-co-glycolide) acid (PLGA); T cell activation score; cytotoxic T lymphocyte (CTL); glioma; major histocompatibility complex (MHC)

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