2. Academic Validation
  3. BTN3A1 governs antitumor responses by coordinating αβ and γδ T cells

BTN3A1 governs antitumor responses by coordinating αβ and γδ T cells

  • Science. 2020 Aug 21;369(6506):942-949. doi: 10.1126/science.aay2767.
Kyle K Payne 1,  Jessica A Mine 1,  Subir Biswas 1,  Ricardo A Chaurio 1,  Alfredo Perales-Puchalt 2,  Carmen M Anadon 1,  Tara Lee Costich 1,  Carly M Harro 1 3,  Jennifer Walrath 2,  Qianqian Ming 4,  Evgenii Tcyganov 2,  Andrea L Buras 5,  Kristen E Rigolizzo 1,  Gunjan Mandal 1,  Jason Lajoie 6,  Michael Ophir 6,  Julia Tchou 7,  Douglas Marchion 8,  Vincent C Luca 4,  Piotr Bobrowicz 6,  Brooke McLaughlin 6,  Ugur Eskiocak 6,  Michael Schmidt 6,  Juan R Cubillos-Ruiz 9,  Paulo C Rodriguez 1,  Dmitry I Gabrilovich 2,  Jose R Conejo-Garcia 10 5
Affiliations

Affiliations

  • 1 Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
  • 2 Immunology, Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA 19104, USA.
  • 3 Department of Cell Biology, Microbiology, and Molecular Biology and Cancer Biology PhD Program, University of South Florida, Tampa, FL 33620, USA.
  • 4 Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
  • 5 Department of Gynecologic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
  • 6 Compass Therapeutics, Cambridge, MA 02142, USA.
  • 7 Division of Endocrine and Oncologic Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, PA 19104-1693, USA.
  • 8 Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
  • 9 Department of Obstetrics and Gynecology, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA.
  • 10 Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. [email protected].
PMID: 32820120 DOI: 10.1126/science.aay2767
Abstract

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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-P99179
    98.95%, CD277 Antibody