Ntrk1 Promotes Resistance to PD-1 Checkpoint Blockade in Mesenchymal Kras/p53 Mutant Lung Cancer.
PD-1/PD-L1 checkpoint blockade
immunotherapy
non-small cell lung cancer
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
02 Apr 2019
02 Apr 2019
Historique:
received:
23
01
2019
revised:
26
03
2019
accepted:
27
03
2019
entrez:
17
4
2019
pubmed:
17
4
2019
medline:
17
4
2019
Statut:
epublish
Résumé
The implementation of cancer immunotherapeutics for solid tumors including lung cancers has improved clinical outcomes in a small percentage of patients. However, the majority of patients show little to no response or acquire resistance during treatment with checkpoint inhibitors delivered as a monotherapy. Therefore, identifying resistance mechanisms and novel combination therapy approaches is imperative to improve responses to immune checkpoint inhibitors. To address this, we performed an in vivo shRNA dropout screen that focused on genes encoding for FDA-approved drug targets (FDAome). We implanted epithelial and mesenchymal Kras/p53 (KP) mutant murine lung cancer cells expressing the FDAome shRNA library into syngeneic mice treated with an anti-PD-1 antibody. Sequencing for the barcoded shRNAs revealed
Identifiants
pubmed: 30986992
pii: cancers11040462
doi: 10.3390/cancers11040462
pmc: PMC6521201
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : Cancer Prevention and Research Institute of Texas
ID : RP160652-P3
Organisme : University of Texas MD Anderson Cancer Center
ID : CCSG CA016672
Organisme : NCI NIH HHS
ID : P50 CA070907
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA214609
Pays : United States
Organisme : NIH HHS
ID : CA214609-01A1
Pays : United States
Références
J Neurosci Res. 2000 Feb 1;59(3):356-64
pubmed: 10679771
J Clin Oncol. 2005 Sep 1;23(25):5900-9
pubmed: 16043828
J Biol Chem. 2006 Jun 9;281(23):15636-44
pubmed: 16611639
Annu Rev Immunol. 2008;26:677-704
pubmed: 18173375
PLoS One. 2009;4(4):e5401
pubmed: 19404390
Genes Dev. 2009 Sep 15;23(18):2140-51
pubmed: 19759262
Nature. 2011 May 5;473(7345):101-4
pubmed: 21471965
Nat Rev Cancer. 2012 Mar 22;12(4):252-64
pubmed: 22437870
N Engl J Med. 2012 Jun 28;366(26):2443-54
pubmed: 22658127
N Engl J Med. 2012 Jun 28;366(26):2455-65
pubmed: 22658128
Nat Med. 2013 Nov;19(11):1469-1472
pubmed: 24162815
Annu Rev Med. 2014;65:185-202
pubmed: 24188664
Nat Commun. 2014 Oct 28;5:5241
pubmed: 25348003
Nature. 2014 Nov 27;515(7528):568-71
pubmed: 25428505
Cancer Discov. 2015 Aug;5(8):860-77
pubmed: 26069186
Oncoimmunology. 2015 Apr 1;4(7):e1016700
pubmed: 26140242
N Engl J Med. 2015 Oct 22;373(17):1627-39
pubmed: 26412456
J Thorac Oncol. 2015 Dec;10(12):1670-4
pubmed: 26565381
Cancer Discov. 2016 Jan;6(1):OF4
pubmed: 26603524
Sci Rep. 2016 Jan 05;6:18652
pubmed: 26728244
Cancer Discov. 2016 Jan;6(1):14-6
pubmed: 26747892
Nat Commun. 2016 Feb 17;7:10501
pubmed: 26883990
Nat Rev Clin Oncol. 2016 Apr;13(4):202-3
pubmed: 26977783
Int Immunol. 2016 Aug;28(8):383-91
pubmed: 26989092
Cell. 2016 Mar 24;165(1):35-44
pubmed: 26997480
Oral Oncol. 2016 Jul;58:59-70
pubmed: 27215705
Cell Rep. 2016 Jun 28;16(1):133-147
pubmed: 27320920
N Engl J Med. 2016 Sep 1;375(9):819-29
pubmed: 27433843
Oncogene. 2017 Apr 6;36(14):1925-1938
pubmed: 27694892
ESMO Open. 2016 Mar 18;1(2):e000023
pubmed: 27843590
Nature. 2017 Jul 27;547(7664):413-418
pubmed: 28723893
Nature. 2017 Aug 31;548(7669):537-542
pubmed: 28783722
Cancer Discov. 2018 Jul;8(7):822-835
pubmed: 29773717
Cancer Discov. 2018 Sep;8(9):1156-1175
pubmed: 30012853
Sci Transl Med. 2019 Mar 13;11(483):null
pubmed: 30867319