Work

BTN2A1 acquisition through trogocytosis enhances Vγ9Vδ2 T cell cytotoxicity against autologous and cancer cells

Year: 2025

Type: article

Abstract: Butyrophilins (BTNs) are emerging as novel druggable immune targets in oncology, promoting the activation of gamma delta (γδ) T cells against cancer cells. Therapies targeting BTN3A or BTN2A1 are under development, but their regulation is poorly understood. Here, we report that lymphocytes' BTN2A1 expression increases with CD3/CD28 stimulation, mediated by trogocytosis in the presence of activated myeloid cells. For instance, BTN2A1 can be acquired by the BTN2A1-knockout (BTN2A1KO) B cell line through trogocytosis when cultured with monocytes. In addition, cytotoxicity assays determine that BTN2A1-acquired normal or tumor cells exhibit higher sensitivity to Vγ9Vδ2 T cell lysis. 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.

Source: Cell Reports

DOI: 10.1016/j.celrep.2025.116387