Faculty Opinions recommendation of Genome-wide CRISPR-Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1.
Year: 2020
Type: peer-review
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 (MAIT) 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 patient T cells enabled killing of autologous and non-autologous melanoma.These findings offer opportunities for HLA-independent, pan-cancer, pan-population immunotherapies.
Authors: Sergei Koralov, Elitza Ivanova
Institutions: NYU Langone Health, New York University
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4255397502