Abstract
Background: γδ T cells represent a unique T cell subpopulation due to their ability to recognize cancer cells in a T cell receptor- (TCR) dependent manner, but also in a non-major histocompatibility complex- (MHC) restricted way via natural killer receptors (NKRs). Endowed with these features, they represent attractive effectors for immuno-therapeutic strategies with a better safety profile and a more favorable anti-tumor efficacy in comparison to conventional αβ T cells. Also, remarkable progress has been achieved re-activating exhausted T lymphocytes with inhibitors of co-regulatory receptors e.g., programmed cell death protein 1 (PD-1), T cell immunoreceptor with Ig and ITIM domains (TIGIT) and of the adenosine pathway (CD39, CD73). Regarding γδ T cells, little evidence is available. This study aimed to immunophenotypically characterize γδ T cells from patients with diagnosed acute myeloid leukemia (AML) in comparison to patients with multiple myeloma (MM) and healthy donors (HD).Methods: The frequency, differentiation, activation, and exhaustion status of bone marrow- (BM) derived γδ T cells from patients with AML (n = 10) and MM (n = 11) were assessed in comparison to corresponding CD4+ and CD8+ T cells and peripheral blood- (PB) derived γδ T cells from HDs (n = 16) using multiparameter flow cytometry.Results: BM-infiltrating Vδ1 T cells showed an increased terminally differentiated cell population (TEMRAs) in AML and MM in comparison to HDs with an aberrant subpopulation of CD27−CD45RA++ cells. TIGIT, PD-1, TIM-3, and CD39 were more frequently expressed by γδ T cells in comparison to the corresponding CD4+ T cell population, with expression levels that were similar to that on CD8+ effector cells in both hematologic malignancies. In comparison to Vδ2 T cells, the increased frequency of PD-1+-, TIGIT+-, TIM-3+, and CD39+ cells was specifically observed on Vδ1 T cells and related to the TEMRA Vδ1 population with a significant co-expression of PD-1 and TIM-3 together with TIGIT.Conclusion: Our results revealed that BM-resident γδ T cells in AML and MM express TIGIT, PD-1, TIM-3 and CD39. As effector population for autologous and allogeneic strategies, inhibition of co-inhibitory receptors on especially Vδ1 γδ T cells may lead to re-invigoration that could further increase their cytotoxic potential.
Highlights
Γδ T cells represent a relatively small subset within all T lymphocytes (1–5%) [1, 2], they have a unique property to recognize cancer cells in a T cell receptor- (TCR) dependent manner and in a non- major histocompatibility complex(MHC) restricted way via their expression of natural killer cell receptors (NKRs) [3]
bone marrow (BM)-Derived Vδ1 T Cells of non-acute promyelocytic leukemia (AML) and multiple myeloma (MM) Patients Show a Shift Toward Effector Memory- and Terminally Differentiated Memory Cells γδ T cells were analyzed in the BM from patients with AML (n = 10) and MM (n = 11) in comparison to the peripheral blood (PB) from age-matched healthy donor (HD) (n = 16)
As illustrated in the t-distributed stochastic neighbor embedding analysis (Figure 1C), the distribution of Vδ1 and Vδ2 γδ T cells differed between HD, AML and MM: Vδ2 T cells were more prevalent in the PB in HDs compared to the BM compartment in AML and MM (Figure 1D)
Summary
Γδ T cells represent a relatively small subset within all T lymphocytes (1–5%) [1, 2], they have a unique property to recognize cancer cells in a T cell receptor- (TCR) dependent manner and in a non- major histocompatibility complex(MHC) restricted way via their expression of natural killer cell receptors (NKRs) [3]. Vδ2 cells constitute the major circulating γδ T cell population in the peripheral blood (PB) whereas the Vδ1 subpopulation is enriched in the peripheral tissue [4, 5] Both γδ subpopulations exhibit cytotoxic capacities mediated by TCR- and natural killer group 2D (NKG2D) receptor signaling via production of the effector cytokines interferon (IFN)-γ, tumor necrosis factor (TNF)-α and soluble mediators such as perforin or granzymes [5,6,7]. Γδ T cells can induce dendritic cell (DC) maturation via secretion of TNF-α [8, 9] They have an antigenpresenting capacity by MHC-II loading and expression [10]. Recent data demonstrate a phagocytic potential of γδ T cells through expression of the scavenger receptor CD36 which is dependent on the transcription factor CCAAT-enhancer-binding protein α (C/EBPα) [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
