ABSTRACT
The diverse structural and functional heterogeneity of γδ T cells is related to their distinct role in cancer immunity. The different phenotypes of γδ 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 γδ T cells remains unknown. In this study, we analyzed the distribution of γδ 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 (including de novo AML, AML in non-remission (NR), and AML in complete remission (CR)). Our data demonstrated an imbalanced distribution of TIGIT and CD226 on γδ T cells with a decrease in CD226+ γδ T cells and an increase in TIGIT+ γδ T cells in de novo AML patients, while TIGIT−CD226+ γδ T cells were restored in AML patients who achieved CR after chemotherapy. Moreover, the patients who had higher TIGIT+CD226− γδ 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.
Abbreviations: AML: acute myeloid leukemia; CR: complete remission; ICs: immune checkpoints; PD-1: programmed death-1; γδ T cells: gamma delta T cells; TCR: T cell receptor; MHC: major histocompatibility complex; TIGIT: T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain; NK: natural killer; PB: Peripheral blood; NR: non-remission; FAB: French-American-British; WHO: World Health Organization; HIs: healthy individuals; OS: overall survival
Acknowledgments
We want to acknowledge the Flow Facility of Biological Translational Research Institute of Jinan University, and we also would like to thank the healthy volunteers who donated blood for this project. We thank professor Yi Zhang from Temple University, who gave valuable comments and helped to edit the article.
Authors’ contributions
YQL, XLW and XYZ contributed to the concept development and study design. ZYJ, TBL, XL, and SHC performed the laboratory studies. JC and JL collected the clinical data. ZYJ, TBL, YZ, and JXD participated in the manuscript and figure preparation. YQL coordinated the study and helped draft the manuscript.
Competing interests
The authors have no financial conflict of interest regarding this study.
Ethics approval and consent to participate
PB samples were obtained from the Department of the Clinical Laboratory, First Affiliated Hospital of Jinan University. This study was conducted according to the guidelines of the Medical Ethics Committees of the Health Bureau of the Guangdong Province in China and was approved by ethical approval of the Ethics Committee of the First Affiliated Hospital of Jinan University.
Data availability statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supplementary material
Supplemental data for this article can be accessed on the publisher’s website.