CD8+ T cells expressing both PD-1 and TIGIT but not CD226 are dysfunctional in acute myeloid leukemia (AML) patients
2017
Abstract Acute myeloid leukemia (AML) is one of the most common types of leukemia among adults with an overall poor prognosis and very limited treatment management.
Immune checkpointblockade of PD-1 alone or combined with other
immune checkpointblockade has gained impressive results in murine AML models by improving anti-leukemia
CD8+ T cell function, which has greatly promoted the strategy to utilize combined
immune checkpointinhibitors to treat AML patients. However, the expression profiles of these
immune checkpointreceptors, such as co-inhibitory receptors PD-1 and
TIGITand co-stimulatory receptor
CD226, in T cells from AML patients have not been clearly defined. Here we have defined subsets of
CD8+ and CD4 + T cells in the peripheral blood (PB) from newly diagnosed AML patients and healthy controls (HCs). We have observed increased frequencies of PD-1- and
TIGIT- expressing
CD8+ T cells but decreased occurrence of
CD226-expressing
CD8+ T cells in AML patients. Further analysis of these
CD8+ T cells revealed a unique
CD8+ T cell subset that expressed PD-1 and
TIGITbut displayed lower levels of
CD226was associated with failure to achieve remission after
induction chemotherapyand FLT3-ITD mutations which predict poor clinical prognosis in AML patients. Importantly, these PD-1 +
TIGIT+
CD226−
CD8+ T cells are dysfunctional with lower expression of intracellular IFN-γ and TNF-α than their counterparts in HCs. Therefore, our studies revealed that an increased frequency of a unique
CD8+ T cell subset, PD-1 +
TIGIT+
CD226−
CD8+ T cells, is associated with
CD8+ T cell dysfunction and poor clinical prognosis of AML patients, which may reveal critical diagnostic or prognostic biomarkers and direct more efficient therapeutic strategies.
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