Butyrophilins: Dynamic Regulators of Protective T Cell Immunity in Cancer

Rinkee Kumari, Elaheh Sadat Hosseini, Kristen E. Warrington, Tyler Milonas, Kyle K. Payne

Research output: Contribution to journalReview articlepeer-review


The efficacy of current immunotherapies remains limited in many solid epithelial malignancies. Recent investigations into the biology of butyrophilin (BTN) and butyrophilin-like (BTNL) molecules, however, suggest these molecules are potent immunosuppressors of antigen-specific protective T cell activity in tumor beds. BTN and BTNL molecules also associate with each other dynamically on cellular surfaces in specific contexts, which modulates their biology. At least in the case of BTN3A1, this dynamism drives the immunosuppression of αβ T cells or the activation of Vγ9Vδ2 T cells. Clearly, there is much to learn regarding the biology of BTN and BTNL molecules in the context of cancer, where they may represent intriguing immunotherapeutic targets that could potentially synergize with the current class of immune modulators in cancer. Here, we discuss our current understanding of BTN and BTNL biology, with a particular focus on BTN3A1, and potential therapeutic implications for cancer.

Original languageEnglish (US)
Article number8722
JournalInternational journal of molecular sciences
Issue number10
StatePublished - May 2023
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


  • butyrophilins
  • immune oncology
  • immune suppression
  • immunotherapy
  • γδ T cells


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