INCREASED TIGIT+ CD226- ΓΔ T CELLS ARE ASSOCIATED WITH DIFFERENT CLINICAL STATUS IN AML

Abstract

Adoptive immunotherapy is gaining momentum to fight acute myeloid leukemia (AML), whereby γδ T cells have diverse structural and functional heterogeneity which may help to set up the strategy to utilize combined immune checkpoint inhibitors to treat AML patients. The novel immune checkpoint co-inhibitor TIGIT shares similar ligands as the co-stimulatory receptor CD226 and suppresses T cell response by limiting CD226 activation. However, the expression profiles of these receptors and their significance in γδ T cells from AML patients have not been defined clearly. Here we have defined subpopulations of γδ T cells in peripheral blood from AML patients (including 14 cases of de novo AML, 4 cases of recurrent AML and 7 cases in complete remission (CR)) and 19 age-sex-matched healthy individuals (HIs) by the flow cytometry. CD226+γδ T cells were decreased, while TIGIT+γδ T cells were increased in de novo AML group. Moreover, the proportions of Foxp3+γδ T cells, Foxp3+CD226-γδ T cells, TIGIT+Foxp3+γδ T cells, TIGIT+γδ T cells and TIGIT+CD226- γδ T cells were significantly higher either in both de novo or the recurrent AML groups, and showed the pattern as the recurrent AML > the de novo AML > the AML-CR > HIs groups. In contrast, CD226+ TIGIT- or Foxp3-CD226+γδ T cells were associated with clinical status showing the pattern as HIs > the AML-CR > the recurrent AML > the de novo AML. Phenotypic and functional abnormalities of TIGIT+ γδ T cells and TIGIT+ CD226- γδ T cells were partially restored in 4 cases with de novo AML who achieved CR after chemotherapy. In conclusion, we firstly characterized different TIGIT+ γδ T cell subset in AML, increased TIGIT+CD226-γδ T cells may influence clinical outcome in patients with AML. This may be considered to evaluate their role as immune biomarker for AML immunotherapy.