Characteristic of TIGIT and DNAM-1 Expression on Foxp3+ γδ T Cells in AML Patients.

Foxp3+gamma delta regulatory T (gamma delta Treg) cells promote tumor growth by various mechanisms and induce immuno-senescence. The novel immune checkpoint coinhibitory receptor T cell Ig and ITIM domain (TIGIT) shares similar ligands as the costimulatory receptor DNAX accessory molecule 1 (DNAM-1) and suppresses T cell responses in tumor patients. This study is aimed at characterizing whether the TIGIT/DNAM-1 axis is involved in the distribution and expression of Foxp3+gamma delta Treg cell subsets in acute myeloid leukemia (AML) patients of different clinical statuses:de novoAML (27 patients), AML in nonremission (NR) (7 patients), and AML in complete remission (CR) (12 patients). Our data demonstrated that the proportions of Foxp3+, TIGIT+Foxp3+, and DNAM-1+Foxp3+gamma delta T cells are significantly higher inde novoand NR patients. High levels of TIGIT and DNAM-1 on Foxp3+gamma delta T cells correlated with increased Foxp3+gamma delta T cell frequencies. In addition, a high TIGIT/DNAM-1 ratio was observed inde novoAML patients and healthy individuals (HIs). Furthermore, the phenotypic abnormalities in Foxp3+, TIGIT+Foxp3+, and DNAM-1+Foxp3+gamma delta T cells were restored when the patients achieved CR after chemotherapy. Moreover, higher TIGIT+Foxp3+gamma delta T cells were associated with AML patients who had poor overall survival and were an independent risk factor for prognosis. In conclusion, our study reveals for the first time that the TIGIT/DNAM-1 axis may be involved in Foxp3+gamma delta Treg cells and indicates the clinical progression and prognosis of AML patients of different clinical statuses, which is considered beneficial for efficient AML immunotherapy.