Higher TIGIT⁺CD226^- γδ T cells in Patients with Acute Myeloid Leukemia

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

KEYWORDS:

• Acute myeloid leukemia
• γδ T cells
• TIGIT
• CD226

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.

Additional information

Funding

This study was supported by grant from the National Natural Science Foundation of China (Nos. 81800143, 81770150, 91642111, and 81770152); Natural Science Foundation of Guangdong Province (Nos. 2018A0303130220 and 2020A1515010817); the China Postdoctoral Science Foundation (Nos. 2018M643374 and 2018M640884); the Guangzhou Science and Technology Project (Nos. 201804010425, 201807010004, and 201803040017); Guangdong Provincial Applied Science and Technology Research and Development Program (No. 2016B020237006); Medical Scientific Research Foundation of Guangdong Province (Nos. A2018565 and A2017198); the National Training Program of Innovation and Entrepreneurship for Undergraduates (Nos. 201910559089 and 202010559079) and the Training Program of Innovation and Entrepreneurship for Undergraduates (Nos. CX2019116 and CX2019099).