In this section
@article{Weterings:2026:10.1016/j.bneo.2026.100235,
author = {Weterings, DA and Chiou, Yee LL and Watber, P and Baylon, J and Greiller, C and Taylor, GP and Cook, LB and Rowan, AG},
doi = {10.1016/j.bneo.2026.100235},
journal = {Blood Neoplasia},
title = {Loss of HTLV-1–specific CD8 T-cell immunity in virus-carriers predisposed to adult T-cell leukemia/lymphoma},
url = {http://dx.doi.org/10.1016/j.bneo.2026.100235},
year = {2026}
}
TY - JOUR
AB - Adult T-cell Leukemia/Lymphoma (ATL) is caused by chronic infection with Human T-lymphotropic virus type-1 (HTLV-1). HTLV-1 contains highly immunogenic CD8+ T-cell epitopes which elicit high frequencies of virus-specific CD8+ T-cells in most virus-carriers. Despite the virus being present in the tumour, HTLV-1-specific CD8+ cells are often undetectable in ATL. To characterise HTLV-1-specific CD8+ T-cells during ATL development, we studied a sub-group of people living with asymptomatic HTLV-1 infection at very high risk of developing ATL. These so- called ‘high-risk’ carriers have suspected premalignant lesions: expanded, HTLV-1-infected ‘ATL-like’ clones circulating in their peripheral blood. Compared to viral antigen-burden matched controls, high-risk carriers had significantly fewer Tax-specific IFN-γ+CD8+ cells in peripheral blood. Furthermore, ex vivo CD8+ T-cells from high-risk carriers did not efficiently kill autologous HTLV-1-infected T-cells, including premalignant ATL-like clones. We stained Tax11–19/HLA-A0201 pentamer+CD8+ T-cells to test whether the low frequencies of functional CD8+ T-cells resulted from the phenotype or absolute frequency of HTLV-1-specific CD8+ T-cells. Again, high-risk carriers had significantly lower frequencies of Tax11–19/HLA-A0201 pentamer+CD8+ T-cells than controls, but we observed no difference in effector function, memory phenotype or expression of checkpoint control molecules (PD-1, TIGIT, TIM-3, LAG-3, CTLA-4). In contrast, there was no difference in the frequency of CD8+ T-cells specific for other viruses (CMV, EBV, Flu) between high-risk carriers and controls. This is the first report of HTLV-1-specific immune dysregulation in the premalignant stage of ATL. Low frequencies of HTLV-1-specific CD8+ T-cells may contribute to ATL development, and may be a novel therapeutic target for ATL prevention.
AU - Weterings,DA
AU - Chiou,Yee LL
AU - Watber,P
AU - Baylon,J
AU - Greiller,C
AU - Taylor,GP
AU - Cook,LB
AU - Rowan,AG
DO - 10.1016/j.bneo.2026.100235
PY - 2026///
SN - 2950-3280
TI - Loss of HTLV-1–specific CD8 T-cell immunity in virus-carriers predisposed to adult T-cell leukemia/lymphoma
T2 - Blood Neoplasia
UR - http://dx.doi.org/10.1016/j.bneo.2026.100235
UR - https://doi.org/10.1016/j.bneo.2026.100235
ER -