Science: Reveals the mechanism by which protein BTN3A1 regulates anti-tumor immune response.

August 29, 2020 // ---T cells are immune cells that can be activated by their gamma or alpha beta-beta-beins, which can be divided into gamma-T cells and alpha-beta-T cells.
both types of T-cells are found in most human cancers, but current immunotherapy does not take advantage of their synergetic anti-tumor activity. The activation of
t-T cells can be caused by butyrophilin and lactose-like molecules, which are structurally similar to members of the immunosuppressive B7 family, but how they regulate and coordinate alpha beta T cell responses and gamma-T cell responses remains unknown.
a new study, researchers from several U.S. research institutions found that BTN3A1 and BTN2A1, two members of the lactose lipoprotein family, worked together to activate the most abundant subpopulation of gamma T cells in the outer blood.
study was published in the August 21, 2020 issue of the Journal of Science under the title "BTN3A1 Governs antitumor responses by coordinating alpha beta and t-cells."
images from Science, 2020, doi:10.1126/science.aay2767.
authors also report that lactose-thyoprotein BTN3A1 inhibits the activation of tumor-reactive alpha beta T cell receptors by preventing N-glycosylated CD45 from falling off immune synapses.
they found that CD277-specific antibodies converted BTN3A1 from immunosuppressive molecules into immunostatification molecules, dynamically inducing coordinated anti-tumor immune responses driven by alpha beta T cells and gamma T cells, thereby preventing the progression of ovarian cancer.
specifically, CD277-specific antibodies can co-restore the effect activity of alpha beta T cells and the lethal effect of BTN2A1-dependent gamma T cells on BTN3A1-positive cancer cells.
antibodies that target BTN3A1 can reboot gamma T cells to attack cancer cells, while also increasing the activity of tumor-specific alpha beta T cells.
therefore, targeting BTN3A1 can coordinate the co-killing of alpha beta T cells and gamma T cells against formed tumors, which may provide a new treatment strategy for tumors that are resistant to existing immunotherapy.
(bioon.com) Reference: Kyle K. Payne et al. BTN3A1 governs antitumor responses by coordinating alpha beta and t cells. Science, 2020, doi:10.1126/science.aay2767.