Genome-wide CRISPR–Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Genome-wide CRISPR–Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1. / Crowther, Michael D.; Dolton, Garry; Legut, Mateusz; Caillaud, Marine E.; Lloyd, Angharad; Attaf, Meriem; Galloway, Sarah A.E.; Rius, Cristina; Farrell, Colin P.; Szomolay, Barbara; Ager, Ann; Parker, Alan L.; Fuller, Anna; Donia, Marco; McCluskey, James; Rossjohn, Jamie; Svane, Inge Marie; Phillips, John D.; Sewell, Andrew K.

In: Nature Immunology, Vol. 21, No. 2, 2020, p. 178-185.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Crowther, MD, Dolton, G, Legut, M, Caillaud, ME, Lloyd, A, Attaf, M, Galloway, SAE, Rius, C, Farrell, CP, Szomolay, B, Ager, A, Parker, AL, Fuller, A, Donia, M, McCluskey, J, Rossjohn, J, Svane, IM, Phillips, JD & Sewell, AK 2020, 'Genome-wide CRISPR–Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1', Nature Immunology, vol. 21, no. 2, pp. 178-185. https://doi.org/10.1038/s41590-019-0578-8

APA

Crowther, M. D., Dolton, G., Legut, M., Caillaud, M. E., Lloyd, A., Attaf, M., Galloway, S. A. E., Rius, C., Farrell, C. P., Szomolay, B., Ager, A., Parker, A. L., Fuller, A., Donia, M., McCluskey, J., Rossjohn, J., Svane, I. M., Phillips, J. D., & Sewell, A. K. (2020). Genome-wide CRISPR–Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1. Nature Immunology, 21(2), 178-185. https://doi.org/10.1038/s41590-019-0578-8

Vancouver

Crowther MD, Dolton G, Legut M, Caillaud ME, Lloyd A, Attaf M et al. Genome-wide CRISPR–Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1. Nature Immunology. 2020;21(2):178-185. https://doi.org/10.1038/s41590-019-0578-8

Author

Crowther, Michael D. ; Dolton, Garry ; Legut, Mateusz ; Caillaud, Marine E. ; Lloyd, Angharad ; Attaf, Meriem ; Galloway, Sarah A.E. ; Rius, Cristina ; Farrell, Colin P. ; Szomolay, Barbara ; Ager, Ann ; Parker, Alan L. ; Fuller, Anna ; Donia, Marco ; McCluskey, James ; Rossjohn, Jamie ; Svane, Inge Marie ; Phillips, John D. ; Sewell, Andrew K. / Genome-wide CRISPR–Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1. In: Nature Immunology. 2020 ; Vol. 21, No. 2. pp. 178-185.

Bibtex

@article{6df2237e492c4e39ad985c48e78a5d7a,
title = "Genome-wide CRISPR–Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1",
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.",
author = "Crowther, {Michael D.} and Garry Dolton and Mateusz Legut and Caillaud, {Marine E.} and Angharad Lloyd and Meriem Attaf and Galloway, {Sarah A.E.} and Cristina Rius and Farrell, {Colin P.} and Barbara Szomolay and Ann Ager and Parker, {Alan L.} and Anna Fuller and Marco Donia and James McCluskey and Jamie Rossjohn and Svane, {Inge Marie} and Phillips, {John D.} and Sewell, {Andrew K.}",
note = "Author Correction: https://doi.org/10.1038/s41590-020-0640-6",
year = "2020",
doi = "10.1038/s41590-019-0578-8",
language = "English",
volume = "21",
pages = "178--185",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "nature publishing group",
number = "2",

}

RIS

TY - JOUR

T1 - Genome-wide CRISPR–Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1

AU - Crowther, Michael D.

AU - Dolton, Garry

AU - Legut, Mateusz

AU - Caillaud, Marine E.

AU - Lloyd, Angharad

AU - Attaf, Meriem

AU - Galloway, Sarah A.E.

AU - Rius, Cristina

AU - Farrell, Colin P.

AU - Szomolay, Barbara

AU - Ager, Ann

AU - Parker, Alan L.

AU - Fuller, Anna

AU - Donia, Marco

AU - McCluskey, James

AU - Rossjohn, Jamie

AU - Svane, Inge Marie

AU - Phillips, John D.

AU - Sewell, Andrew K.

N1 - Author Correction: https://doi.org/10.1038/s41590-020-0640-6

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

UR - https://doi.org/10.1038/s41590-020-0640-6

U2 - 10.1038/s41590-019-0578-8

DO - 10.1038/s41590-019-0578-8

M3 - Journal article

C2 - 31959982

AN - SCOPUS:85078152760

VL - 21

SP - 178

EP - 185

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

IS - 2

ER -

ID: 235774868