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Functional Change of Effector Tumor-Infiltrating CCR5+CD38+HLA-DR+CD8+ T Cells in Glioma Microenvironment
- Source :
- Frontiers in Immunology, Vol 10 (2019), Frontiers in Immunology
- Publication Year :
- 2019
- Publisher :
- Frontiers Media S.A., 2019.
-
Abstract
- Human glioma facilitates an impaired anti-tumor immunity response, including defects in circulation of T lymphocytes. The level of CD8+ T-cell activation acts as an immune regulator associated with disease progression. However, little is known about the characteristics of peripheral and tumor-infiltrating CD8+ T cells in patients with glioma. In this study, we examined the level of CD8+ T-cell activation in a group of 143 patients with glioma and determined that peripheral CD3+ T cells decreased in accordance with disease severity. The patients' peripheral CD8+ T-cell populations were similar to that of healthy donors, and a small amount of CD8+ tumor-infiltrating lymphocytes was identified in glioma tissues. An increase in activated CD8+ T cells, characterized as CD38+HLA-DR+, and their association with disease progression were identified in the patients' peripheral blood and glioma, and shown to display enriched CCR5+ and TNFR2+ expression levels. Ex vivo examination of CD38+HLA-DR+CD8+ T cells indicated that this subset of cells displayed stronger secretion of IFN-γ and IL-2 before and after a 6-h stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin (ION) relative to healthy CD38+HLA-DR+CD8+ T cells, indicating the functional feasibility of CD38+HLA-DR+CD8+ T cells. Higher CCL5 protein and mRNA levels were identified in glioma tissues, which was consistent with the immunohistochemistry results revealing both CCL5 and CD38+HLA-DR+CD8+ T cell expression. Patients' CCR5+CD38+HLA-DR+CD8+ T cells were further validated and shown to display increases in CD45RA+CCR7- and T-bet+ accompanied by substantial CD107-a, IFN-γ, and Granzyme B levels in response to glioma cells.
- Subjects :
- 0301 basic medicine
Adult
Male
lcsh:Immunologic diseases. Allergy
Receptors, CCR5
T cell
CD3
Immunology
CD38
CD8-Positive T-Lymphocytes
CCL5
03 medical and health sciences
0302 clinical medicine
Immune system
glioma
medicine
Tumor Microenvironment
Cytotoxic T cell
Humans
Immunology and Allergy
Original Research
Membrane Glycoproteins
biology
Chemistry
hemic and immune systems
HLA-DR Antigens
CD8
Middle Aged
Molecular biology
ADP-ribosyl Cyclase 1
Granzyme B
030104 developmental biology
medicine.anatomical_structure
biology.protein
Female
lcsh:RC581-607
CCR5
030215 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 16643224
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....c08df9c33eb440283516ad2d803eafde
- Full Text :
- https://doi.org/10.3389/fimmu.2019.02395/full