PMID- 31959982
OWN - NLM
STAT- MEDLINE
DCOM- 20200413
LR  - 20240328
IS  - 1529-2916 (Electronic)
IS  - 1529-2908 (Print)
IS  - 1529-2908 (Linking)
VI  - 21
IP  - 2
DP  - 2020 Feb
TI  - Genome-wide CRISPR-Cas9 screening reveals ubiquitous T cell cancer targeting via 
      the monomorphic MHC class I-related protein MR1.
PG  - 178-185
LID - 10.1038/s41590-019-0578-8 [doi]
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.
FAU - Crowther, Michael D
AU  - Crowther MD
AD  - Division of Infection and Immunity, Cardiff University School of Medicine, 
      Cardiff, UK.
FAU - Dolton, Garry
AU  - Dolton G
AD  - Division of Infection and Immunity, Cardiff University School of Medicine, 
      Cardiff, UK.
FAU - Legut, Mateusz
AU  - Legut M
AD  - Division of Infection and Immunity, Cardiff University School of Medicine, 
      Cardiff, UK.
FAU - Caillaud, Marine E
AU  - Caillaud ME
AD  - Division of Infection and Immunity, Cardiff University School of Medicine, 
      Cardiff, UK.
FAU - Lloyd, Angharad
AU  - Lloyd A
AD  - Division of Infection and Immunity, Cardiff University School of Medicine, 
      Cardiff, UK.
FAU - Attaf, Meriem
AU  - Attaf M
AD  - Division of Infection and Immunity, Cardiff University School of Medicine, 
      Cardiff, UK.
FAU - Galloway, Sarah A E
AU  - Galloway SAE
AD  - Division of Infection and Immunity, Cardiff University School of Medicine, 
      Cardiff, UK.
FAU - Rius, Cristina
AU  - Rius C
AD  - Division of Infection and Immunity, Cardiff University School of Medicine, 
      Cardiff, UK.
FAU - Farrell, Colin P
AU  - Farrell CP
AD  - Division of Hematology, University of Utah School of Medicine, Salt Lake City, 
      UT, USA.
FAU - Szomolay, Barbara
AU  - Szomolay B
AD  - Division of Infection and Immunity, Cardiff University School of Medicine, 
      Cardiff, UK.
AD  - Systems Immunity Research Institute, Cardiff University, Cardiff, UK.
FAU - Ager, Ann
AU  - Ager A
AD  - Division of Infection and Immunity, Cardiff University School of Medicine, 
      Cardiff, UK.
AD  - Systems Immunity Research Institute, Cardiff University, Cardiff, UK.
FAU - Parker, Alan L
AU  - Parker AL
AUID- ORCID: 0000-0002-9302-1761
AD  - Division of Cancer and Genetics, Cardiff University School of Medicine, Cardiff, 
      UK.
FAU - Fuller, Anna
AU  - Fuller A
AD  - Division of Infection and Immunity, Cardiff University School of Medicine, 
      Cardiff, UK.
FAU - Donia, Marco
AU  - Donia M
AUID- ORCID: 0000-0003-4966-9752
AD  - Center for Cancer Immune Therapy, Herlev Hospital, Copenhagen University, 
      Copenhagen, Denmark.
FAU - McCluskey, James
AU  - McCluskey J
AUID- ORCID: 0000-0002-8597-815X
AD  - Department of Microbiology and Immunology, Peter Doherty Institute for Infection 
      and Immunity, University of Melbourne, Parkville, Victoria, Australia.
FAU - Rossjohn, Jamie
AU  - Rossjohn J
AUID- ORCID: 0000-0002-2020-7522
AD  - Division of Infection and Immunity, Cardiff University School of Medicine, 
      Cardiff, UK.
AD  - Systems Immunity Research Institute, Cardiff University, Cardiff, UK.
AD  - Australian Research Council Centre of Excellence in Advanced Molecular Imaging, 
      Monash University, Clayton, Victoria, Australia.
AD  - Infection and Immunity Program & Department of Biochemistry and Molecular 
      Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 
      Australia.
FAU - Svane, Inge Marie
AU  - Svane IM
AD  - Center for Cancer Immune Therapy, Herlev Hospital, Copenhagen University, 
      Copenhagen, Denmark.
FAU - Phillips, John D
AU  - Phillips JD
AD  - Division of Hematology, University of Utah School of Medicine, Salt Lake City, 
      UT, USA.
FAU - Sewell, Andrew K
AU  - Sewell AK
AUID- ORCID: 0000-0003-3194-3135
AD  - Division of Infection and Immunity, Cardiff University School of Medicine, 
      Cardiff, UK. sewellak@cardiff.ac.uk.
AD  - Systems Immunity Research Institute, Cardiff University, Cardiff, UK. 
      sewellak@cardiff.ac.uk.
LA  - eng
GR  - 24416/CRUK_/Cancer Research UK/United Kingdom
GR  - U54 DK110858/DK/NIDDK NIH HHS/United States
GR  - 100327/WT_/Wellcome Trust/United Kingdom
GR  - MR/L008742/1/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200120
PL  - United States
TA  - Nat Immunol
JT  - Nature immunology
JID - 100941354
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (MR1 protein, human)
RN  - 0 (Minor Histocompatibility Antigens)
RN  - 0 (Receptors, Antigen, T-Cell)
SB  - IM
CIN - Nat Immunol. 2020 Feb;21(2):108-110. PMID: 31959981
CIN - Nat Rev Immunol. 2020 Mar;20(3):141. PMID: 32024985
EIN - Nat Immunol. 2020 Mar 2;:. PMID: 32123375
MH  - Animals
MH  - CRISPR-Cas Systems
MH  - Cytotoxicity, Immunologic/*immunology
MH  - Genome-Wide Association Study
MH  - Histocompatibility Antigens Class I/*immunology
MH  - Humans
MH  - Immunotherapy/methods
MH  - Lymphocyte Activation/immunology
MH  - Mice
MH  - Minor Histocompatibility Antigens/*immunology
MH  - Neoplasms/*immunology
MH  - Receptors, Antigen, T-Cell/*immunology
MH  - T-Lymphocyte Subsets/*immunology
PMC - PMC6983325
MID - EMS85172
COIS- Competing Interests Cardiff University has filed patents based on these findings.
EDAT- 2020/01/22 06:00
MHDA- 2020/04/14 06:00
PMCR- 2020/07/20
CRDT- 2020/01/22 06:00
PHST- 2019/02/15 00:00 [received]
PHST- 2019/12/10 00:00 [accepted]
PHST- 2020/01/22 06:00 [pubmed]
PHST- 2020/04/14 06:00 [medline]
PHST- 2020/01/22 06:00 [entrez]
PHST- 2020/07/20 00:00 [pmc-release]
AID - 10.1038/s41590-019-0578-8 [pii]
AID - 10.1038/s41590-019-0578-8 [doi]
PST - ppublish
SO  - Nat Immunol. 2020 Feb;21(2):178-185. doi: 10.1038/s41590-019-0578-8. Epub 2020 
      Jan 20.