
BTN3A1 governs antitumor responses by coordinating αβ and γδ T cells.
Gamma delta (γδ) T cells infiltrate most human tumors, but current immunotherapies fail to exploit their in situ major histocompatibility complex-independent tumoricidal potential. Activation of γδ T cells can be elicited by butyrophilin and butyrophilin-like molecules that are structurally similar to the immunosuppressive B7 family members, yet how they regulate and coordinate αβ and γδ T cell responses remains unknown. Here, we report that the butyrophilin BTN3A1 inhibits tumor-reactive αβ T cell receptor activation by preventing segregation of N-glycosylated CD45 from the immune synapse. Notably, CD277-specific antibodies elicit coordinated restoration of αβ T cell effector activity and BTN2A1-dependent γδ lymphocyte cytotoxicity against BTN3A1+ cancer cells, abrogating malignant progression. Targeting BTN3A1 therefore orchestrates cooperative killing of established tumors by αβ and γδ T cells and may present a treatment strategy for tumors resistant to existing immunotherapies.
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Related Subject Headings
- Xenograft Model Antitumor Assays
- Tumor Cells, Cultured
- Receptors, Antigen, T-Cell, alpha-beta
- Ovarian Neoplasms
- Mice, Transgenic
- Mice
- Intraepithelial Lymphocytes
- Immunotherapy
- Humans
- General Science & Technology
Citation

Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Xenograft Model Antitumor Assays
- Tumor Cells, Cultured
- Receptors, Antigen, T-Cell, alpha-beta
- Ovarian Neoplasms
- Mice, Transgenic
- Mice
- Intraepithelial Lymphocytes
- Immunotherapy
- Humans
- General Science & Technology