IFNγ enhances cytotoxic efficiency of the cytotoxic T lymphocytes against human glioma cells
| Autor: | Lingeng Lu, Wenxue Ma, Danielle Burner, Boris Minev, Eric Risch, Shengwen Shao |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cytotoxicity Immunologic Enzyme-Linked Immunospot Assay T cell Immunology chemical and pharmacologic phenomena Human leukocyte antigen Major histocompatibility complex Lymphocyte Activation Immunotherapy Adoptive 03 medical and health sciences Interferon-gamma 0302 clinical medicine Antigens Neoplasm Cell Line Tumor MHC class I HLA-A2 Antigen medicine Immunology and Allergy Cytotoxic T cell Humans Antigen-presenting cell Pharmacology Antigen Presentation biology ELISPOT Dendritic Cells Glioma Up-Regulation Gene Expression Regulation Neoplastic 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis biology.protein CD8 T-Lymphocytes Cytotoxic |
| Zdroj: | International immunopharmacology. 47 |
| ISSN: | 1878-1705 |
| Popis: | 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 p = 0.022). These findings suggest that a clinical application of IFNγ treatment may have potential benefits. |
| Databáze: | OpenAIRE |
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