Higher TIGIT(+)CD226(-) gamma delta T cells in Patients with Acute Myeloid Leukemia

The diverse structural and functional heterogeneity of gamma delta T cells is related to their distinct role in cancer immunity. The different phenotypes of gamma delta T cells in patients with acute myeloid leukemia (AML) is far from clear. In particular, the expression pattern of co-inhibitory and co-stimulatory receptors on gamma delta T cells remains unknown. In this study, we analyzed the distribution of gamma delta T cell subsets by expression of the immune checkpoint co-inhibitor TIGIT (T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain) and its competing co-stimulatory receptor CD226 in AML patients of different clinical statuses (includingde novoAML, AML in non-remission (NR), and AML in complete remission (CR)). Our data demonstrated an imbalanced distribution of TIGIT and CD226 on gamma delta T cells with a decrease in CD226(+)gamma delta T cells and an increase in TIGIT(+)gamma delta T cells inde novoAML patients, while TIGIT(-)CD226(+)gamma delta T cells were restored in AML patients who achieved CR after chemotherapy. Moreover, the patients who had higher TIGIT(+)CD226(-)gamma delta T cells showed lower overall survival rate for non-M3 AML, which may be considered a novel prognostic immune biomarker. In conclusion, our study reveals for the first time that imbalance in the TIGIT/CD226 axis might be related to different clinical outcomes for AML patients.