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BTN3A1 governs antitumor responses by coordinating αβ and γδ T cells.

Publication ,  Journal Article
Payne, KK; Mine, JA; Biswas, S; Chaurio, RA; Perales-Puchalt, A; Anadon, CM; Costich, TL; Harro, CM; Walrath, J; Ming, Q; Tcyganov, E ...
Published in: Science
August 21, 2020

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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Published In

Science

DOI

EISSN

1095-9203

Publication Date

August 21, 2020

Volume

369

Issue

6506

Start / End Page

942 / 949

Location

United States

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

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Payne, K. K., Mine, J. A., Biswas, S., Chaurio, R. A., Perales-Puchalt, A., Anadon, C. M., … Conejo-Garcia, J. R. (2020). BTN3A1 governs antitumor responses by coordinating αβ and γδ T cells. Science, 369(6506), 942–949. https://doi.org/10.1126/science.aay2767
Payne, Kyle K., Jessica A. Mine, Subir Biswas, Ricardo A. Chaurio, Alfredo Perales-Puchalt, Carmen M. Anadon, Tara Lee Costich, et al. “BTN3A1 governs antitumor responses by coordinating αβ and γδ T cells.Science 369, no. 6506 (August 21, 2020): 942–49. https://doi.org/10.1126/science.aay2767.
Payne KK, Mine JA, Biswas S, Chaurio RA, Perales-Puchalt A, Anadon CM, et al. BTN3A1 governs antitumor responses by coordinating αβ and γδ T cells. Science. 2020 Aug 21;369(6506):942–9.
Payne, Kyle K., et al. “BTN3A1 governs antitumor responses by coordinating αβ and γδ T cells.Science, vol. 369, no. 6506, Aug. 2020, pp. 942–49. Pubmed, doi:10.1126/science.aay2767.
Payne KK, Mine JA, Biswas S, Chaurio RA, Perales-Puchalt A, Anadon CM, Costich TL, Harro CM, Walrath J, Ming Q, Tcyganov E, Buras AL, Rigolizzo KE, Mandal G, Lajoie J, Ophir M, Tchou J, Marchion D, Luca VC, Bobrowicz P, McLaughlin B, Eskiocak U, Schmidt M, Cubillos-Ruiz JR, Rodriguez PC, Gabrilovich DI, Conejo-Garcia JR. BTN3A1 governs antitumor responses by coordinating αβ and γδ T cells. Science. 2020 Aug 21;369(6506):942–949.
Journal cover image

Published In

Science

DOI

EISSN

1095-9203

Publication Date

August 21, 2020

Volume

369

Issue

6506

Start / End Page

942 / 949

Location

United States

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