Targeting butyrophilins for cancer immunotherapy

Vγ9Vδ2⁺ T cells form part of the innate immune repertoire and are activated by phosphorylated antigens produced by many bacteria and tumors. They have long been suggested as promising targets for anti-tumor therapies, but clinical trials so far have not shown major successes. Several recent discoveries could help to overcome these shortfalls, such as those leading to an improved understanding of the role of butyrophilin molecules BTN2A1 and BTN3A1, in Vγ9Vδ2⁺ T cell activation. Moreover, we propose that studies suggesting the presence of live bacteria in a variety of tumors (tumor microbiome), indicate that the latter might be harnessed as a source of high affinity bacterial phosphoantigen to trigger or enhance anti-tumor immune responses.