作者
Matthias Braun, Amelia Roman Aguilera, Ashmitha Sundarrajan, Dillon Corvino, Kimberley Stannard, Sophie Krumeich, Indrajit Das, Luize G Lima, Lizeth G Meza Guzman, Kunlun Li, Rui Li, Nazhifah Salim, Maria Villancanas Jorge, Sunyoung Ham, Gabrielle Kelly, Frank Vari, Ailin Lepletier, Ashwini Raghavendra, Sally Pearson, Jason Madore, Sebastien Jacquelin, Maike Effern, Brodie Quine, Lambros T Koufariotis, Mika Casey, Kyohei Nakamura, Eun Y Seo, Michael Hölzel, Matthias Geyer, Glen Kristiansen, Touraj Taheri, Elizabeth Ahern, Brett GM Hughes, James S Wilmott, Georgina V Long, Richard A Scolyer, Martin D Batstone, Jennifer Landsberg, Dimo Dietrich, Oltin T Pop, Lukas Flatz, William C Dougall, Andre Veillette, Sandra E Nicholson, Andreas Möller, Robert J Johnston, Ludovic Martinet, Mark J Smyth, Tobias Bald
发表日期
2020/10/13
期刊
Immunity
卷号
53
期号
4
页码范围
805-823. e15
出版商
Elsevier
简介
The activating receptor CD226 is expressed on lymphocytes, monocytes, and platelets and promotes anti-tumor immunity in pre-clinical models. Here, we examined the role of CD226 in the function of tumor-infiltrating lymphocytes (TILs) and resistance to immunotherapy. In murine tumors, a large proportion of CD8+ TILs had decreased surface expression of CD226 and exhibited features of dysfunction, whereas CD226hi TILs were highly functional. This correlation was seen also in TILs isolated from HNSCC patients. Mutation of CD226 at tyrosine 319 (Y319) led to increased CD226 surface expression, enhanced anti-tumor immunity and improved efficacy of immune checkpoint blockade (ICB). Mechanistically, tumor-derived CD155, the ligand for CD226, initiated phosphorylation of Y319 by Src kinases, thereby enabling ubiquitination of CD226 by CBL-B, internalization, and proteasomal degradation. In pre …
学术搜索中的文章
M Braun, AR Aguilera, A Sundarrajan, D Corvino… - Immunity, 2020