Butyrophilins: γδ T Cell Receptor Ligands, Immunomodulators and More

Herrmann, Thomas; Karunakaran, Mohindar Murugesh

doi:10.3389/fimmu.2022.876493

Cited by 26 publications

(19 citation statements)

References 40 publications

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“…It has recently gained increased attention that, in human as well as in mouse, different butyrophilin and butyrophilin-like (BTNL) molecules are important in the activation/antigen recognition by γδ T cells. Examples in the human are the BTN2A1 and BTN3A1 for phosphoantigens by Vγ9Vδ2 γδ T cells as well as BTNL3/8 by resident Vγ4 γδ T cells in the gut epithelium [78][79][80][81]. It would be worth investigating the abundance of various BTN and BTNL molecules at the MFI which could prompt the TRGV2 enrichment detected in early decidua thanks to the expected interaction between the γδ TCR the BTN/BTNL and their antigen/ligand(s).…”

Section: Discussionmentioning

confidence: 99%

Human decidual gamma/delta T cells possess unique effector and TCR repertoire profiles during pregnancy

Manchorova

Papadopoulou

Alexandrova

et al. 2022

Cellular Immunology

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Section: Discussionmentioning

confidence: 99%

Human decidual gamma/delta T cells possess unique effector and TCR repertoire profiles during pregnancy

Manchorova

Papadopoulou

Alexandrova

et al. 2022

Cellular Immunology

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“…The TCR‐dependent recognition of PAg by the Vγ9Vδ2 T cells requires the presence of members of the Ig‐like butyrophilin family of transmembrane molecules, specifically BTN3A1 and BTN2A1. Intracellular PAg bind to the B30.2 signalling domain of BTN3A1, thereby inducing in concert with BTN2A1 a conformational change which is then recognized by the γδ TCR 43,45–51 . This process involves additional molecules such as RhoB, a small molecule with GTPase‐activity which stabilizes BTN3A1 in the membrane 51 .…”

Section: Immune Surveillance In Gbm: the Role Of Cd8 Ctl γδ T Cells A...mentioning

confidence: 99%

Immune surveillance in glioblastoma: Role of the NKG2D system and novel cell‐based therapeutic approaches

Chitadze

Kabelitz

2022

Scand J Immunol

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Glioblastoma, formerly known as glioblastoma multiforme (GBM), is the most frequent and most aggressive brain tumour in adults. The brain is an immunopriviledged organ, and the blood-brain barrier shields the brain from immune surveillance. In this review, we discuss the composition of the immunosuppressive tumour micromilieu and potential immune escape mechanisms in GBM. In this respect, we focus on the role of the NKG2D receptor/ligand system. NKG2D ligands are frequently expressed on GBM tumour cells and can activate NKG2Dexpressing killer cells including NK cells and γδ T cells. Soluble NKG2D ligands, however, contribute to tumour escape from immunological attack. We also discuss the current immunotherapeutic strategies to improve the survival of GBM patients. Such approaches include the modulation of the NKG2D receptor/ligand system, the application of checkpoint inhibitors, the adoptive transfer of ex vivo expanded and/or modified immune cells or the application of antibodies and antibody constructs to target cytotoxic effector cells in vivo. In view of the multitude of pursued strategies, there is hope for improved overall survival of GBM patients in the future. F I G U R E 1Treatment protocol of patients with newly diagnosed GBM. Radiochemotherapy (RCT) is applied according to the Stupps protocol following surgery (60 Gy splitted up on 2 Gy for 5 days a week in 6 cycles plus chemotherapy with temozolomide [TMZ] at 75 mg/ m 2 body surface during radiation). Following RCT, at least 6 cycles of chemotherapy with TMZ at a dose of 150-200 mg/m 2 body surface on 5 of 28 days are applied. Whenever applicable, tumour-treating fields (TTFs) are administered together with TMZ until reoccurrence of the disease How to cite this article: Chitadze G, Kabelitz D. Immune surveillance in glioblastoma: Role of the NKG2D system and novel cell-based therapeutic approaches.

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“…These conserved and non-alloreactive unconventional T lymphocytes are selectively activated in a TCR/CD3-dependent, but MHC-independent, manner by non-peptidic small metabolites of isoprenoid synthesis pathways called PAg (phosphoantigen), such as IPP (isopentenyl pyrophosphate). This peculiar and exquisitely specific stress sensing process, which remains ill defined, also involves BTN (butyrophilin)3A/BTN2A molecules which are expressed at the surface of target cells (3)(4)(5). The sensitization of target cells with elevated pinocytic activity by pharmacological NBP (aminobisphosphonate) compounds, such as zoledronate, which inhibit a key IPP-degrading enzyme of the mammalian mevalonate pathway, upregulate the reactivity of Vg9Vd2 T lymphocytes (6).…”

Section: Introductionmentioning

confidence: 99%

The antitumor activity of human Vγ9Vδ2 T cells is impaired by TGF-β through significant phenotype, transcriptomic and metabolic changes

et al. 2023

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Despite significant advances, the eradication of cancer remains a clinical challenge which justifies the urgent exploration of additional therapeutic strategies such as immunotherapies. Human peripheral Vγ9Vδ2 T cells represent an attractive candidate subset for designing safe, feasible and effective adoptive T cell transfer-based therapies. However, following their infiltration within tumors, γδ T cells are exposed to various regulating constituents and signals from the tumor microenvironment (TME), which severely alter their antitumor functions. Here, we show that TGF-β, whose elevated production in some solid tumors is linked to a poor prognosis, interferes with the antigenic activation of human Vγ9Vδ2 T cells in vitro. This regulatory cytokine strongly impairs their cytolytic activity, which is accompanied by the induction of particular phenotypic, transcriptomic and metabolic changes. Collectively, these observations provide information for better understanding and targeting the impact of TME components to regulate the antitumor activity of human T cell effectors.

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Butyrophilins: γδ T Cell Receptor Ligands, Immunomodulators and More

Cited by 26 publications

References 40 publications

Human decidual gamma/delta T cells possess unique effector and TCR repertoire profiles during pregnancy

Human decidual gamma/delta T cells possess unique effector and TCR repertoire profiles during pregnancy

Immune surveillance in glioblastoma: Role of the NKG2D system and novel cell‐based therapeutic approaches

The antitumor activity of human Vγ9Vδ2 T cells is impaired by TGF-β through significant phenotype, transcriptomic and metabolic changes

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