Functional Phenotypes of Human Vγ9Vδ2 T Cells in Lymphoid Stress Surveillance

Nussbaumer, Oliver; Thurnher, Martin

doi:10.3390/cells9030772

Cited by 17 publications

(21 citation statements)

References 90 publications

(118 reference statements)

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“… 148 , 155 , 156 IL-15 has also been shown to upregulate the expression of CD56, 157 which is known to be expressed on γδ T cells with potent cytotoxic activity. 51 , 158 We also observed the upregulation of CD56 on Vδ2T cells by IL-15. 159 Cytokines other than common γ-chain cytokines also modulate the cytotoxic potential of γδ T cells.…”

Section: How To Improve the In Vitro Expansion And Effector Activity supporting

confidence: 54%

“… 49 While it is to be expected that more specific ligands for various γδ T cell subsets will be identified in the future, the emerging overall picture clearly indicates that the TCR of γδ T cells is constantly being scrutinized for signs of “stress” on normal cells and those undergoing malignant transformation, thereby assigning γδ T cells an important place in local immune surveillance. 50 , 51 This conclusion is well supported by a pivotal study demonstrating an increased susceptibility to tumor development in γδ T cell deficient mice. 52 …”

Section: Ligand Recognition By Human γδ T Cellsmentioning

confidence: 74%

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Cancer immunotherapy with γδ T cells: many paths ahead of us

et al. 2020

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γδ T cells play uniquely important roles in stress surveillance and immunity for infections and carcinogenesis. Human γδ T cells recognize and kill transformed cells independently of human leukocyte antigen (HLA) restriction, which is an essential feature of conventional αβ T cells. Vγ9Vδ2 γδ T cells, which prevail in the peripheral blood of healthy adults, are activated by microbial or endogenous tumor-derived pyrophosphates by a mechanism dependent on butyrophilin molecules. γδ T cells expressing other T cell receptor variable genes, notably Vδ1, are more abundant in mucosal tissue. In addition to the T cell receptor, γδ T cells usually express activating natural killer (NK) receptors, such as NKp30, NKp44, or NKG2D which binds to stress-inducible surface molecules that are absent on healthy cells but are frequently expressed on malignant cells. Therefore, γδ T cells are endowed with at least two independent recognition systems to sense tumor cells and to initiate anticancer effector mechanisms, including cytokine production and cytotoxicity. In view of their HLA-independent potent antitumor activity, there has been increasing interest in translating the unique potential of γδ T cells into innovative cellular cancer immunotherapies. Here, we discuss recent developments to enhance the efficacy of γδ T cell-based immunotherapy. This includes strategies for in vivo activation and tumor-targeting of γδ T cells, the optimization of in vitro expansion protocols, and the development of gene-modified γδ T cells. It is equally important to consider potential synergisms with other therapeutic strategies, notably checkpoint inhibitors, chemotherapy, or the (local) activation of innate immunity.

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Section: How To Improve the In Vitro Expansion And Effector Activity supporting

confidence: 54%

Section: Ligand Recognition By Human γδ T Cellsmentioning

confidence: 74%

Cancer immunotherapy with γδ T cells: many paths ahead of us

et al. 2020

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“…for Vg9Vd2 T cells (22,59,60). To investigate whether these phenotypic changes actually corresponded to changes in functionality, we compared the cytotoxic capacity of Vg9Vd2 T cells expanded for 9 days versus those expanded for 14 or 25 days.…”

Section: Discussionmentioning

confidence: 99%

Vγ9Vδ2 T Cells Concurrently Kill Cancer Cells and Cross-Present Tumor Antigens

et al. 2021

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The human Vγ9Vδ2 T cell is a unique cell type that holds great potential in immunotherapy of cancer. In particular, the therapeutic potential of this cell type in adoptive cell therapy (ACT) has gained interest. In this regard optimization of in vitro expansion methods and functional characterization is desirable. We show that Vγ9Vδ2 T cells, expanded in vitro with zoledronic acid (Zometa or ZOL) and Interleukin-2 (IL-2), are efficient cancer cell killers with a trend towards increased killing efficacy after prolonged expansion time. Thus, Vγ9Vδ2 T cells expanded for 25 days in vitro killed prostate cancer cells more efficiently than Vγ9Vδ2 T cells expanded for 9 days. These data are supported by phenotype characteristics, showing increased expression of CD56 and NKG2D over time, reaching above 90% positive cells after 25 days of expansion. At the early stage of expansion, we demonstrate that Vγ9Vδ2 T cells are capable of cross-presenting tumor antigens. In this regard, our data show that Vγ9Vδ2 T cells can take up tumor-associated antigens (TAA) gp100, MART-1 and MAGE-A3 - either as long peptide or recombinant protein – and then present TAA-derived peptides on the cell surface in the context of HLA class I molecules, demonstrated by their recognition as targets by peptide-specific CD8 T cells. Importantly, we show that cross-presentation is impaired by the proteasome inhibitor lactacystin. In conclusion, our data indicate that Vγ9Vδ2 T cells are broadly tumor-specific killers with the additional ability to cross-present MHC class I-restricted peptides, thereby inducing or supporting tumor-specific αβTCR CD8 T cell responses. The dual functionality is dynamic during in vitro expansion, yet, both functions are of interest to explore in ACT for cancer therapy.

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“…It is known that Vγ9Vδ2 T cells are the major subset of γδ T cells in human PBMCs 12 . According to the marker knowledge of γδ T cells [12][13][14] , we define the TRGV9 + TRDV2 + subpopulation as Vγ9Vδ2 T cells and other CD161(KLRB1) + TRGC1 + TRGC2 + cells as γδ T cells. The γδ T cells also express canonical γδ T cell markers CCR5, CCR6 15 as well as SLC4A10 16 and TRAV1-2 17 , which are known as Mucosal-associated invariant T (MAIT) cell markers.…”

Section: Meta-analysis Reveals Common Cell Types and Tissue-specific mentioning

confidence: 99%

Meta-analysis reveals consistent immune response patterns in COVID-19 infected patients at single-cell resolution

Garg

Moreno

et al. 2021

Preprint

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A number of single-cell RNA studies looking at the human immune response to the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been recently published. However, the number of samples used in each individual study typically is small, moreover the technologies and protocols used in different studies vary, thus somewhat restricting the range of conclusions that can be made with high confidence. To better capture the cellular gene expression changes upon SARS-CoV-2 infection at different levels and stages of disease severity and to minimise the effect of technical artefacts, we performed meta-analysis of data from 9 previously published studies, together comprising 143 human samples, and a set of 16 healthy control samples (10X). In particular, we used generally accepted immune cell markers to discern specific cell subtypes and to look at the changes of the cell proportion over different disease stages and their consistency across the studies. While half of the observations reported in the individual studies can be confirmed across multiple studies, half of the results seem to be less conclusive. In particular, we show that the differentially expressed genes consistently point to upregulation of type I Interferon signal pathway and downregulation of the mitochondrial genes, alongside several other reproducibly consistent changes. We also confirm the presence of expanded B-cell clones in COVID-19 patients, however, no consistent trend in T-cell clonal expansion was observed.

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Functional Phenotypes of Human Vγ9Vδ2 T Cells in Lymphoid Stress Surveillance

Cited by 17 publications

References 90 publications

Cancer immunotherapy with γδ T cells: many paths ahead of us

Cancer immunotherapy with γδ T cells: many paths ahead of us

Vγ9Vδ2 T Cells Concurrently Kill Cancer Cells and Cross-Present Tumor Antigens

Meta-analysis reveals consistent immune response patterns in COVID-19 infected patients at single-cell resolution

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