Low-Density Lipoprotein Uptake Inhibits the Activation and Antitumor Functions of Human Vγ9Vδ2 T Cells.
Loading...
Embargo End Date
ICR Authors
Authors
Rodrigues, NV
Correia, DV
Mensurado, S
Nóbrega-Pereira, S
deBarros, A
Kyle-Cezar, F
Tutt, A
Hayday, AC
Norell, H
Silva-Santos, B
Dias, S
Correia, DV
Mensurado, S
Nóbrega-Pereira, S
deBarros, A
Kyle-Cezar, F
Tutt, A
Hayday, AC
Norell, H
Silva-Santos, B
Dias, S
Document Type
Journal Article
Date
2018-04-01
Date Accepted
2018-01-08
Abstract
Vγ9Vδ2 T cells, the main subset of γδ T lymphocytes in human peripheral blood, are endowed with antitumor functions such as cytotoxicity and IFNγ production. These functions are triggered upon T-cell receptor-dependent activation by non-peptidic prenyl pyrophosphates ("phosphoantigens") that are selective agonists of Vγ9Vδ2 T cells, and which have been evaluated in clinical studies. Because phosphoantigens have shown interindividual variation in Vγ9Vδ2 T-cell activities, we asked whether metabolic resources, namely lipids such as cholesterol, could affect phosphoantigen-mediated Vγ9Vδ2 T-cell activation and function. We show here that Vγ9Vδ2 T cells express the LDL receptor upon activation and take up LDL cholesterol. Resulting changes, such as decreased mitochondrial mass and reduced ATP production, correlate with downregulation of Vγ9Vδ2 T-cell activation and functionality. In particular, the expression of IFNγ, NKG2D, and DNAM-1 were reduced upon LDL cholesterol treatment of phosphoantigen-expanded Vγ9Vδ2 T cells. As a result, their capacity to target breast cancer cells was compromised both in vitro and in an in vivo xenograft mouse model. Thus, this study describes the role of LDL cholesterol as an inhibitor of the antitumor functions of phosphoantigen-activated Vγ9Vδ2 T cells. Our observations have implications for therapeutic applications dependent on Vγ9Vδ2 T cells. Cancer Immunol Res; 6(4); 448-57. ©2018 AACR.
Citation
Cancer immunology research, 2018, 6 (4), pp. 448 - 457
Source Title
Cancer immunology research
Publisher
AMER ASSOC CANCER RESEARCH
ISSN
2326-6066
eISSN
2326-6074
Collections
Research Team
Directorate Breast Canc