BTN3A1 governs antitumor responses by coordinating αβ and γδ T cells

doi:10.1126/science.aay2767

GSTDTAP > 气候变化

DOI	10.1126/science.aay2767
	BTN3A1 governs antitumor responses by coordinating αβ and γδ T cells
	Kyle K. Payne; Jessica A. Mine; Subir Biswas; Ricardo A. Chaurio; Alfredo Perales-Puchalt; Carmen M. Anadon; Tara Lee Costich; Carly M. Harro; Jennifer Walrath; Qianqian Ming; Evgenii Tcyganov; Andrea L. Buras; Kristen E. Rigolizzo; Gunjan Mandal; Jason Lajoie; Michael Ophir; Julia Tchou; Douglas Marchion; Vincent C. Luca; Piotr Bobrowicz; Brooke McLaughlin; Ugur Eskiocak; Michael Schmidt; Juan R. Cubillos-Ruiz; Paulo C. Rodriguez; Dmitry I. Gabrilovich; Jose R. Conejo-Garcia
	2020-08-21
发表期刊	Science
出版年	2020
英文摘要	T lymphocytes are immune cells that can be activated through their gamma delta (γδ) or alpha beta (αβ) receptors. Both T cell types are found in human cancers, but current immunotherapies do not harness their coordinated antitumor activity. Payne et al. found that BTN3A1 and BTN2A1, two members of the butyrophilin family of proteins, partner to activate the most abundant subset of γδ T cells in peripheral blood. Antibodies targeting BTN3A1 redirect γδ T cells to attack cancer cells while also increasing the activity of tumor-specific αβ T cells. Thus, the killing of established tumors by different T cell subsets can be achieved through BTN3A1 targeting and may provide new strategies for cancer immunotherapy. Science , this issue p. [942][1] 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. [1]: /lookup/doi/10.1126/science.aay2767
领域	气候变化 ; 资源环境
URL	查看原文
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/291213
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Kyle K. Payne,Jessica A. Mine,Subir Biswas,et al. BTN3A1 governs antitumor responses by coordinating αβ and γδ T cells[J]. Science,2020.
APA	Kyle K. Payne.,Jessica A. Mine.,Subir Biswas.,Ricardo A. Chaurio.,Alfredo Perales-Puchalt.,...&Jose R. Conejo-Garcia.(2020).BTN3A1 governs antitumor responses by coordinating αβ and γδ T cells.Science.
MLA	Kyle K. Payne,et al."BTN3A1 governs antitumor responses by coordinating αβ and γδ T cells".Science (2020).