Cytotoxic lymphocytes target characteristic biophysical vulnerabilities in cancer.
Actin Cytoskeleton
/ immunology
Actins
/ immunology
Animals
Cell Communication
/ immunology
Cell Line
Cell Line, Tumor
Cell Movement
/ immunology
Female
HEK293 Cells
Humans
Killer Cells, Natural
/ immunology
Lymphocytes
/ immunology
MCF-7 Cells
Male
Mice
Mice, Inbred C57BL
Neoplasms
/ immunology
Signal Transduction
/ immunology
Transcription Factors
/ immunology
NK cell
T cell
cancer immunology
checkpoint blockade therapy
cytotoxicity
immunosurveillance
mechanobiology
metastasis
myocardin related transcription factor
Journal
Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918
Informations de publication
Date de publication:
11 05 2021
11 05 2021
Historique:
received:
31
03
2020
revised:
16
01
2021
accepted:
25
02
2021
pubmed:
24
3
2021
medline:
15
9
2021
entrez:
23
3
2021
Statut:
ppublish
Résumé
Immune cells identify and destroy tumors by recognizing cellular traits indicative of oncogenic transformation. In this study, we found that myocardin-related transcription factors (MRTFs), which promote migration and metastatic invasion, also sensitize cancer cells to the immune system. Melanoma and breast cancer cells with high MRTF expression were selectively eliminated by cytotoxic lymphocytes in mouse models of metastasis. This immunosurveillance phenotype was further enhanced by treatment with immune checkpoint blockade (ICB) antibodies. We also observed that high MRTF signaling in human melanoma is associated with ICB efficacy in patients. Using biophysical and functional assays, we showed that MRTF overexpression rigidified the filamentous actin cytoskeleton and that this mechanical change rendered mouse and human cancer cells more vulnerable to cytotoxic T lymphocytes and natural killer cells. Collectively, these results suggest that immunosurveillance has a mechanical dimension, which we call mechanosurveillance, that is particularly relevant for the targeting of metastatic disease.
Identifiants
pubmed: 33756102
pii: S1074-7613(21)00086-8
doi: 10.1016/j.immuni.2021.02.020
pmc: PMC8119359
mid: NIHMS1681160
pii:
doi:
Substances chimiques
Actins
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1037-1054.e7Subventions
Organisme : NIAID NIH HHS
ID : R01 AI125651
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA252978
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002003
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA129243
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI087644
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
Références
Annu Rev Genet. 1999;33:29-55
pubmed: 10690403
Biophys J. 2000 Jan;78(1):520-35
pubmed: 10620315
Mol Cell Biol. 2008 Oct;28(20):6302-13
pubmed: 18694962
Cell. 2009 Nov 25;139(5):891-906
pubmed: 19931152
EMBO J. 2017 Feb 15;36(4):520-535
pubmed: 28028053
Science. 2018 Sep 28;361(6409):
pubmed: 30262472
Science. 2009 Jan 30;323(5914):642-4
pubmed: 19179533
Cell Rep. 2018 Apr 3;23(1):227-238.e3
pubmed: 29617662
Immunity. 2011 Aug 26;35(2):161-8
pubmed: 21867926
Dev Cell. 2019 May 6;49(3):332-346
pubmed: 31063753
PLoS One. 2012;7(10):e46609
pubmed: 23056368
Nat Med. 2010 Jan;16(1):116-22
pubmed: 20023634
Cell. 2014 Apr 10;157(2):357-368
pubmed: 24725404
J Cell Biol. 2009 Jun 29;185(7):1275-84
pubmed: 19564406
Science. 2011 Mar 25;331(6024):1565-70
pubmed: 21436444
J Immunol. 2013 May 1;190(9):4661-75
pubmed: 23554309
Cancer Cell. 2012 Dec 11;22(6):709-24
pubmed: 23201163
Cell Syst. 2018 Mar 28;6(3):271-281.e7
pubmed: 29596782
Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2241-6
pubmed: 24469820
Science. 2002 Jul 5;297(5578):63-4
pubmed: 12098689
Biophys J. 2009 May 20;96(10):4326-35
pubmed: 19450503
Cell. 2017 Nov 2;171(4):934-949.e16
pubmed: 29033130
Acta Biomater. 2007 Jul;3(4):413-38
pubmed: 17540628
Science. 2015 Oct 9;350(6257):207-211
pubmed: 26359337
Trends Cell Biol. 2012 Oct;22(10):527-35
pubmed: 22921414
Nat Rev Cancer. 2013 Jan;13(1):3
pubmed: 23258155
Cancer Res. 2014 Sep 1;74(17):4845-4852
pubmed: 25056119
Cancer Cell. 2019 Jul 8;36(1):68-83.e9
pubmed: 31257073
Front Med. 2018 Aug;12(4):361-373
pubmed: 30043221
Cancer Cell. 2018 Apr 9;33(4):676-689.e3
pubmed: 29622463
Nat Protoc. 2009;4(1):44-57
pubmed: 19131956
Proc Natl Acad Sci U S A. 2009 Jun 23;106(25):10290-5
pubmed: 19502425
Mol Cell Oncol. 2018 Mar 7;5(3):e1448244
pubmed: 30250901
Biophys J. 2012 Jan 18;102(2):L5-7
pubmed: 22339876
Annu Rev Immunol. 2019 Apr 26;37:173-200
pubmed: 30550719
Cell. 2016 Mar 24;165(1):45-60
pubmed: 27015306
Nat Genet. 2018 Sep;50(9):1271-1281
pubmed: 30150660
Nat Med. 2019 Dec;25(12):1916-1927
pubmed: 31792460
PLoS One. 2011 May 10;6(5):e19680
pubmed: 21572959
Nature. 2005 Apr 14;434(7035):917-21
pubmed: 15829967
Nat Cell Biol. 2009 Mar;11(3):257-68
pubmed: 19198601
Cancer Cell. 2019 Feb 11;35(2):238-255.e6
pubmed: 30753825
J Biol Chem. 2010 Jul 16;285(29):22036-49
pubmed: 20466732
J Immunol. 1986 Feb 15;136(4):1504-9
pubmed: 3080525
Cell. 2016 Mar 24;165(1):35-44
pubmed: 26997480
Biophys J. 2005 May;88(5):3689-98
pubmed: 15722433
Curr Opin Cell Biol. 2012 Apr;24(2):277-83
pubmed: 22209238
J Exp Med. 2016 Feb 8;213(2):225-33
pubmed: 26755706
Annu Rev Cell Dev Biol. 2007;23:495-517
pubmed: 17506701
Eur J Nucl Med Mol Imaging. 2004 May;31(5):740-51
pubmed: 15014901
Nature. 2019 Apr;568(7753):511-516
pubmed: 30971826
J Biol Chem. 2003 Oct 24;278(43):41977-87
pubmed: 14565952
Nat Protoc. 2012 May 03;7(6):1042-51
pubmed: 22555243
Nat Med. 2018 Oct;24(10):1550-1558
pubmed: 30127393
Genome Res. 2017 Apr;27(4):524-532
pubmed: 28373299
Nat Methods. 2017 May;14(5):479-482
pubmed: 28394337
J Clin Invest. 2010 Jun;120(6):2030-9
pubmed: 20501944
Cancer Discov. 2018 Sep;8(9):1069-1086
pubmed: 30115704
J Exp Med. 2013 Nov 18;210(12):2721-37
pubmed: 24190432
Nature. 2005 Apr 14;434(7035):913-7
pubmed: 15829966
Annu Rev Immunol. 2005;23:225-74
pubmed: 15771571
Mol Cell. 2016 Dec 15;64(6):1048-1061
pubmed: 27867007
Nat Methods. 2013 Dec;10(12):1185-91
pubmed: 24185836
Nat Mater. 2020 Jul;19(7):797-806
pubmed: 32066931
F1000Res. 2017 Nov 29;6:2058
pubmed: 29225789
Nat Immunol. 2019 Oct;20(10):1269-1278
pubmed: 31534240
J Immunol. 2018 Jan 15;200(2):385-391
pubmed: 29311379
Cell. 2015 Jun 18;161(7):1681-96
pubmed: 26091043
Nature. 2015 Oct 1;526(7571):131-5
pubmed: 26416748
Nature. 2017 Oct 12;550(7675):270-274
pubmed: 28976960
Cancer Discov. 2012 May;2(5):401-4
pubmed: 22588877
Annu Rev Immunol. 2011;29:235-71
pubmed: 21219185
Cancer Discov. 2014 Jan;4(1):94-109
pubmed: 24265153
Nat Rev Immunol. 2017 Nov;17(11):679-690
pubmed: 28757604
Nat Rev Mol Cell Biol. 2010 May;11(5):353-65
pubmed: 20414257
Cell. 2019 May 2;177(4):806-819
pubmed: 31051105
Cell. 2018 Apr 5;173(2):400-416.e11
pubmed: 29625055
Cancer Cell. 2012 Dec 11;22(6):725-36
pubmed: 23201165
Science. 2014 Jul 11;345(6193):179-83
pubmed: 24968937
Genome Med. 2020 Feb 26;12(1):21
pubmed: 32102694
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Elife. 2017 Jun 08;6:
pubmed: 28594327
J Cell Biol. 2015 Feb 16;208(4):457-73
pubmed: 25666808
Cancer Metastasis Rev. 2009 Jun;28(1-2):5-14
pubmed: 19153674
Cell Host Microbe. 2019 Jan 9;25(1):73-86.e5
pubmed: 30629922
Oncogene. 2016 Nov 17;35(46):5931-5941
pubmed: 27086930
Nature. 2009 Jun 18;459(7249):1005-9
pubmed: 19421193
Science. 2009 Jan 30;323(5914):638-41
pubmed: 19179532
Sci Transl Med. 2015 Mar 25;7(280):280sr1
pubmed: 25810313
Immunol Rev. 2010 May;235(1):24-34
pubmed: 20536553
Nature. 2007 Oct 18;449(7164):827-34
pubmed: 17943119
Cell. 2018 Apr 5;173(2):291-304.e6
pubmed: 29625048
Science. 2018 Jun 15;360(6394):
pubmed: 29773669
Cell. 2016 Feb 25;164(5):1015-30
pubmed: 26898331
Cell. 2016 Mar 24;165(1):100-110
pubmed: 26924577
Sci Signal. 2013 Apr 02;6(269):pl1
pubmed: 23550210
Biophys J. 2019 Apr 23;116(8):1516-1526
pubmed: 30979550
Biomed Microdevices. 2009 Jun;11(3):557-64
pubmed: 19082733
Nat Rev Microbiol. 2011 Jun;9(6):427-39
pubmed: 21522191
Mol Biol Cell. 2017 Jun 1;28(11):1507-1518
pubmed: 28404749
Nat Cell Biol. 2013 Jul;15(7):807-17
pubmed: 23728425
Cell. 2018 Apr 5;173(2):321-337.e10
pubmed: 29625050
Front Cell Dev Biol. 2018 Feb 28;6:17
pubmed: 29541636
Cell. 2014 Feb 27;156(5):1002-16
pubmed: 24581498
Nat Cell Biol. 2018 Aug;20(8):966-978
pubmed: 30038252
Nat Genet. 2019 Feb;51(2):202-206
pubmed: 30643254
Immunity. 2015 Aug 18;43(2):227-39
pubmed: 26231119
J Cell Sci. 2018 Oct 11;131(19):
pubmed: 30309957
JCO Precis Oncol. 2017 Jun 23;1:
pubmed: 32913971
Sci Adv. 2016 May 27;2(5):e1600200
pubmed: 27386546
J Mol Diagn. 2015 May;17(3):251-64
pubmed: 25801821
Elife. 2020 Jul 27;9:
pubmed: 32720892