BTN2A1 (Butyrophilin Subfamily 2 Member A1)

The GADEKILL γδ T and NK cells were analyzed by flow cytometry for the expression of activating and inhibitory receptors and for cytotoxicity against NB, both with and without dinutuximab-β, at a 1:1 effector-to-target ratio...Finally, NB cell lysis positively correlated with B7H6 and BTN2A1, and B7H6-blocking experiments revealed a significant decrease in target cell lysis when cells highly expressing B7H6 were used as targets. Our study demonstrated the potential antineuroblastoma activity of the GADEKILL, supporting its therapeutic use, particularly in the context of relapsed/refractory R/R HR-NB with low GD2 expression.

LC-MS showed that 6-FM-treated CHO-K1 cells accumulated substantial MPP while risedronate, an inhibitor of farnesyl diphosphate synthase, primarily increased DMAPP/IPP...Both BTN2A1 + BTN3A3-transfected CHO-K1 cells and BTN3A1 knockout K562 cells could detect 6-FM, despite their absence of BTN3A1. Our findings provide evidence that MPP functions as a natural ligand of BTN3A3 and establish a foundation for elucidating biological functions of BTN3A3 complementary to the established BTN3A1 pathway.

Finally, we show that trogocytosis-mediated acquisition of BTN2A1 by circulating lymphocytes involves activated monocytes and is correlated with endometrial cancer stage in a cohort of 87 patients. This study provides new insights about the regulation and functions of BTN2A1 but also highlights the potential impact of trogocytosis in regulating the expression of immune checkpoints in normal and pathological conditions.

This review provides a detailed overview of the historical progress and recent discoveries regarding how Vγ9Vδ2 T cells recognize and target tumor cells. We also discuss the potential of γδ T cells immunotherapy and their role as antitumor agents.

In our analysis, BTN2A1, MICA, and HHLA2 displayed significant potential as antigens for the development of anti-ESCA messenger RNA (mRNA) vaccines. The identification of three stable and reproducible immune subtypes specific to ESCA may prove essential in predicting the outcome of mRNA vaccines.

Our study uncovers a "plier-like gripping" mechanism, where BTN multimers bridge the TCR surface to drive activation. These findings establish a structural foundation for γδ T cell-targeted immunotherapies distinct from αβ T cell strategies reliant on major-histocompatibility-complex-mediated antigen presentation.

Cryo-EM reveals that BTN2A1-BTN3A1-BTN3A2 binds two γδ TCR ectodomains, with one being sandwiched between the IgV domains of BTN2A1 and BTN3A2, while the other interacts with the free BTN2A1 IgV in the complex, as evidenced by functional data. Together, our findings uncover the mechanism of ligand-induced inside-out stabilization of BTN receptor complexes for dimeric activation of γδ TCR.

The institution of Dr. Levy has received research support from National Institutes Health.

However, this additive effect was lost when γ9δ2 TCR-ligand interaction was boosted by pamidronate. This study demonstrates the additive effect of combining OVs and Vγ9Vδ2 TCR-engineered immune cells under suboptimal conditions and supports a combination strategy to enhance the efficacy of both therapeutic modalities.

In this issue, Le Floch and colleagues report a new strategy for enabling γδ T cells to be specifically activated to kill acute lymphoblastic leukemia cells and solid tumor cells using agonistic BTN2A1 antibodies. See related article by Le Floch et al., p. XX .

The present study identified several novel potential drug targets and biomarkers for breast cancer, providing new insights into its diagnosis and treatment. The integration of PPI and druggability evaluations enhances the prioritization of these therapeutic targets, paving the way for future drug development efforts.

Inhibition of SYK or ERK phosphorylation abolished M2 reprogramming upon BTN2A1 engagement. Our findings, derived from an analysis of macrophages from healthy donors and human tumors, underscore the pivotal role of BTN2A1 in immunosuppressive macrophage differentiation and function, offering potential applications in cancer immunotherapy.