Tumour infiltrating lymphocytes and immune-related genes as predictors of outcome in pancreatic adenocarcinoma.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
16
01
2019
accepted:
26
06
2019
entrez:
6
8
2019
pubmed:
6
8
2019
medline:
3
3
2020
Statut:
epublish
Résumé
We investigated the correlation between pancreatic ductal adenocarcinoma patient prognosis and the presence of tumour infiltrating lymphocytes and expression of 521 immune system genes. Intratumoural CD3+, CD8+, and CD20+ lymphocytes were examined by immunohistochemistry in 12 PDAC patients with different outcomes who underwent pancreaticoduodenectomy. The results were correlated with gene expression profile using the digital multiplexed NanoString nCounter analysis system (NanoString Technologies, Seattle, WA, USA). Twenty immune system genes were significantly differentially expressed in patients with a good prognosis relative to patients with a worse prognosis: TLR2 and TLR7 (Toll-like receptor superfamily); CD4, CD37, FOXP3, PTPRC (B cell and T cell signalling); IRF5, IRF8, STAT1, TFE3 (transcription factors); ANP32B, CCND3 (cell cycle); BTK (B cell development); TNF, TNFRF1A (TNF superfamily); HCK (leukocyte function); C1QA (complement system); BAX, PNMA1 (apoptosis); IKBKE (NFκB pathway). Differential expression was more than twice log 2 for TLR7, TNF, C1QA, FOXP3, and CD37. Tumour infiltrating lymphocytes were present at higher levels in samples from patients with better prognosis. Our findings indicate that tumour infiltrating lymphocyte levels and expression level of the immune system genes listed above influence pancreatic ductal adenocarcinoma prognosis. This information could be used to improve selection of best responders to immune inhibitors.
Sections du résumé
BACKGROUND
We investigated the correlation between pancreatic ductal adenocarcinoma patient prognosis and the presence of tumour infiltrating lymphocytes and expression of 521 immune system genes.
METHODS
Intratumoural CD3+, CD8+, and CD20+ lymphocytes were examined by immunohistochemistry in 12 PDAC patients with different outcomes who underwent pancreaticoduodenectomy. The results were correlated with gene expression profile using the digital multiplexed NanoString nCounter analysis system (NanoString Technologies, Seattle, WA, USA).
RESULTS
Twenty immune system genes were significantly differentially expressed in patients with a good prognosis relative to patients with a worse prognosis: TLR2 and TLR7 (Toll-like receptor superfamily); CD4, CD37, FOXP3, PTPRC (B cell and T cell signalling); IRF5, IRF8, STAT1, TFE3 (transcription factors); ANP32B, CCND3 (cell cycle); BTK (B cell development); TNF, TNFRF1A (TNF superfamily); HCK (leukocyte function); C1QA (complement system); BAX, PNMA1 (apoptosis); IKBKE (NFκB pathway). Differential expression was more than twice log 2 for TLR7, TNF, C1QA, FOXP3, and CD37.
DISCUSSION
Tumour infiltrating lymphocytes were present at higher levels in samples from patients with better prognosis. Our findings indicate that tumour infiltrating lymphocyte levels and expression level of the immune system genes listed above influence pancreatic ductal adenocarcinoma prognosis. This information could be used to improve selection of best responders to immune inhibitors.
Identifiants
pubmed: 31381571
doi: 10.1371/journal.pone.0219566
pii: PONE-D-19-01495
pmc: PMC6681957
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0219566Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Br J Surg. 2011 Nov;98(11):1573-80
pubmed: 21739427
Front Immunol. 2018 May 29;9:1185
pubmed: 29896201
Eur J Immunol. 2013 May;43(5):1208-19
pubmed: 23420539
Immunity. 2007 Apr;26(4):503-17
pubmed: 17398124
Hum Pathol. 2017 Oct;68:112-118
pubmed: 28882702
Ann Oncol. 2015 Feb;26(2):259-71
pubmed: 25214542
PLoS One. 2014 May 16;9(5):e95843
pubmed: 24835790
N Engl J Med. 2004 Dec 30;351(27):2817-26
pubmed: 15591335
Arch Biochem Biophys. 2007 Jun 15;462(2):132-9
pubmed: 17321482
Dermatol Surg. 2005 Mar;31(3):318-23
pubmed: 15841634
Pancreas. 2017 Oct;46(9):1180-1187
pubmed: 28902789
Oncoimmunology. 2016 Sep 9;5(11):e1232219
pubmed: 27999742
J Immunol. 2010 Jan 15;184(2):939-46
pubmed: 19966212
Cell Death Dis. 2018 Jul 3;9(7):744
pubmed: 29970908
PLoS One. 2013 Sep 17;8(9):e73968
pubmed: 24069258
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
Br J Cancer. 2010 Apr 13;102(8):1294-9
pubmed: 20332777
Trends Cancer. 2018 Jun;4(6):418-428
pubmed: 29860986
Front Physiol. 2015 Mar 23;6:91
pubmed: 25852576
Cancer Cell. 2009 Oct 6;16(4):336-46
pubmed: 19800578
Cancer Metastasis Rev. 2012 Dec;31(3-4):843-54
pubmed: 22833279
Oncoimmunology. 2016 Sep 9;5(11):e1230578
pubmed: 27999739
Lancet. 2012 Mar 3;379(9818):823-32
pubmed: 22285053
Cancer Biol Ther. 2018 Apr 3;19(4):296-305
pubmed: 29313457
Cancer Immunol Res. 2017 Nov;5(11):978-991
pubmed: 29066497
Breast Cancer Res. 2008;10(4):R73
pubmed: 18755024
Ann Surg Oncol. 2009 Jul;16(7):1852-9
pubmed: 19434456
J Pathol. 2013 Jul;230(3):241-8
pubmed: 23460481
J Pathol. 2013 Jun;230(2):132-47
pubmed: 23460469
PLoS One. 2015 Aug 06;10(8):e0133562
pubmed: 26247463
World J Gastroenterol. 2014 Nov 7;20(41):15049-59
pubmed: 25386053
Nat Commun. 2016 Feb 01;7:10346
pubmed: 26831747
BMC Cancer. 2012 Nov 16;12:527
pubmed: 23157946
Biochem Soc Trans. 2017 Jun 15;45(3):741-750
pubmed: 28620035
Cell. 2007 Jun 29;129(7):1275-86
pubmed: 17570480
Mol Cancer Ther. 2010 Jun;9(6):1788-97
pubmed: 20515950
Nat Immunol. 2007 May;8(5):457-62
pubmed: 17440451
N Engl J Med. 2011 Jun 30;364(26):2507-16
pubmed: 21639808
Front Physiol. 2013 Aug 09;4:210
pubmed: 23950747
Br J Cancer. 2015 Mar 31;112(7):1215-22
pubmed: 25826225
Nat Rev Immunol. 2015 Sep 15;15(9):529-44
pubmed: 26292638
Nature. 2007 Jun 28;447(7148):1087-93
pubmed: 17529967
Curr Top Microbiol Immunol. 2006;311:17-58
pubmed: 17048704
Cancers (Basel). 2014 Oct 21;6(4):2137-54
pubmed: 25337831
PLoS One. 2012;7(2):e31507
pubmed: 22363658
Pancreas. 2004 Jan;28(1):e26-31
pubmed: 14707745
Cancer Res. 2002 Feb 15;62(4):1110-5
pubmed: 11861390
Rheumatology (Oxford). 2010 Jul;49(7):1215-28
pubmed: 20194223
J Cell Sci. 2014 Sep 1;127(Pt 17):3641-8
pubmed: 25128561
BMC Cancer. 2013 Sep 24;13:436
pubmed: 24063854
Cent Eur J Immunol. 2018;43(3):314-324
pubmed: 30588176
Am J Pathol. 2019 Jan;189(1):58-70
pubmed: 30558723
J Clin Oncol. 1988 Mar;6(3):462-8
pubmed: 3162513
Clin Cancer Res. 2011 Apr 1;17(7):1765-75
pubmed: 21233400
Lung Cancer. 2012 Jan;75(1):95-101
pubmed: 21719142
Immunol Rev. 2011 May;241(1):260-8
pubmed: 21488902
Curr Opin Immunol. 2013 Apr;25(2):200-5
pubmed: 23422836
Br J Cancer. 2013 Mar 5;108(4):914-23
pubmed: 23385730
Mol Immunol. 2003 Sep;40(2-4):109-23
pubmed: 12914817
Int J Clin Exp Pathol. 2015 Nov 01;8(11):14608-18
pubmed: 26823784
J Immunol. 2009 Nov 15;183(10):6078-86
pubmed: 19890064
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
World J Clin Oncol. 2017 Jun 10;8(3):230-240
pubmed: 28638792
Br J Cancer. 2013 Jan 15;108(1):155-62
pubmed: 23169287
Breast Cancer Res. 2015 Feb 21;17:23
pubmed: 25848820
Br J Cancer. 2015 Mar 17;112(6):1027-36
pubmed: 25742476
Recent Results Cancer Res. 2009;179:257-70
pubmed: 19230545
Cancer Treat Rev. 2014 May;40(4):513-22
pubmed: 24315741
Ann Gastroenterol Surg. 2018 Jun 22;2(4):274-281
pubmed: 30003190