英国卡迪夫大学Andrew K. Sewell课题组利用全基因组CRISPR–Cas9筛选揭示了通过单态性MHC I类相关蛋白MR1普遍性T细胞肿瘤靶向。这一研究成果于2020年1月20日在线发表在国际学术期刊《自然—免疫学》上。
Title: Genome-wide CRISPR–Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1
Author: Michael D. Crowther, Garry Dolton, Mateusz Legut, Marine E. Caillaud, Angharad Lloyd, Meriem Attaf, Sarah A. E. Galloway, Cristina Rius, Colin P. Farrell, Barbara Szomolay, Ann Ager, Alan L. Parker, Anna Fuller, Marco Donia, James McCluskey, Jamie Rossjohn, Inge Marie Svane, John D. Phillips, Andrew K. Sewell
Issue&Volume: 2020-01-20
Abstract: Human leukocyte antigen (HLA)-independent, T cell–mediated targeting of cancer cells would allow immune destruction of malignancies in all individuals. Here, we use genome-wide CRISPR–Cas9 screening to establish that a T cell receptor (TCR) recognized and killed most human cancer types via the monomorphic MHC class I-related protein, MR1, while remaining inert to noncancerous cells. Unlike mucosal-associated invariant T cells, recognition of target cells by the TCR was independent of bacterial loading. Furthermore, concentration-dependent addition of vitamin B-related metabolite ligands of MR1 reduced TCR recognition of cancer cells, suggesting that recognition occurred via sensing of the cancer metabolome. An MR1-restricted T cell clone mediated in vivo regression of leukemia and conferred enhanced survival of NSG mice. TCR transfer to T cells of patients enabled killing of autologous and nonautologous melanoma. These findings offer opportunities for HLA-independent, pan-cancer, pan-population immunotherapies.
DOI: 10.1038/s41590-019-0578-8
Source: https://www.nature.com/articles/s41590-019-0578-8
Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:31.25
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex
本期文章:《自然—免疫学》:Online/在线发表