Clinical significance and correlation of PD-L1, B7-H3, B7-H4, and TILs in pancreatic cancer.
B7-H3
B7-H4
PD-L1
Pancreatic cancer
Tumor immunity
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
27 May 2022
27 May 2022
Historique:
received:
11
02
2022
accepted:
28
04
2022
entrez:
27
5
2022
pubmed:
28
5
2022
medline:
1
6
2022
Statut:
epublish
Résumé
B7 molecules play significant roles in regulating tumor immunity, but their expression patterns and immuno-biological correlations in pancreatic cancer (PaCa) have not been fully discussed. RNA-sequencing data of B7 molecules of PaCa samples in the Cancer Genome Atlas (TCGA) dataset was downloaded from the UCSC Xena to assess the expression, correlation, and mutation of the B7 family in PaCa. Next, two PaCa tissue microarrays (TMAs, Cat. HPanA150CS02 and HPanA120Su02) were obtained from Outdo BioTech (Shanghai, China). To detect the expression levels of PD-L1, B7-H3 and B7-H4, immunohistochemistry (IHC) staining was performed on these TMAs. Most B7 molecules, including B7-1, B7-2, PD-L1, B7-DC, B7-H2, and B7-H5 exhibited similar expression patterns, but B7-H3, B7-H4, B7-H6, and B7-H7 showed outlier expression patterns compared with other B7 molecules. Besides, B7 molecules were genetically stable and exhibited low alteration frequency. IHC staining indicated PD-L1, B7-H3, and B7-H4 were up-regulated in PaCa tissues and showed uncorrelated expression patterns. Furthermore, high expression of PD-L1 and B7-H3 indicated poor-differentiated grades in PaCa. PD-L1 was positively, but B7-H4 was negatively correlated with CD8+ TILs infiltration in PaCa. Moreover, combined PD-L1 and B7-H4 expression was a novel subtyping strategy in PaCa, namely patients with both high PD-L1 and B7-H4 expression exhibited decreased CD8+ TILs infiltration in tumor tissues. Overall, we systemically analyzed the expression patterns of B7 molecules and proposed a novel subtyping strategy in PaCa. Patients with both high PD-L1 and B7-H4 expression exhibited the immuno-cold phenotype, which may be not suitable for immunotherapy.
Sections du résumé
BACKGROUND
BACKGROUND
B7 molecules play significant roles in regulating tumor immunity, but their expression patterns and immuno-biological correlations in pancreatic cancer (PaCa) have not been fully discussed.
METHODS
METHODS
RNA-sequencing data of B7 molecules of PaCa samples in the Cancer Genome Atlas (TCGA) dataset was downloaded from the UCSC Xena to assess the expression, correlation, and mutation of the B7 family in PaCa. Next, two PaCa tissue microarrays (TMAs, Cat. HPanA150CS02 and HPanA120Su02) were obtained from Outdo BioTech (Shanghai, China). To detect the expression levels of PD-L1, B7-H3 and B7-H4, immunohistochemistry (IHC) staining was performed on these TMAs.
RESULTS
RESULTS
Most B7 molecules, including B7-1, B7-2, PD-L1, B7-DC, B7-H2, and B7-H5 exhibited similar expression patterns, but B7-H3, B7-H4, B7-H6, and B7-H7 showed outlier expression patterns compared with other B7 molecules. Besides, B7 molecules were genetically stable and exhibited low alteration frequency. IHC staining indicated PD-L1, B7-H3, and B7-H4 were up-regulated in PaCa tissues and showed uncorrelated expression patterns. Furthermore, high expression of PD-L1 and B7-H3 indicated poor-differentiated grades in PaCa. PD-L1 was positively, but B7-H4 was negatively correlated with CD8+ TILs infiltration in PaCa. Moreover, combined PD-L1 and B7-H4 expression was a novel subtyping strategy in PaCa, namely patients with both high PD-L1 and B7-H4 expression exhibited decreased CD8+ TILs infiltration in tumor tissues.
CONCLUSION
CONCLUSIONS
Overall, we systemically analyzed the expression patterns of B7 molecules and proposed a novel subtyping strategy in PaCa. Patients with both high PD-L1 and B7-H4 expression exhibited the immuno-cold phenotype, which may be not suitable for immunotherapy.
Identifiants
pubmed: 35624419
doi: 10.1186/s12885-022-09639-5
pii: 10.1186/s12885-022-09639-5
pmc: PMC9137118
doi:
Substances chimiques
B7 Antigens
0
B7-H1 Antigen
0
Biomarkers, Tumor
0
Toll-Like Receptor 1
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
584Informations de copyright
© 2022. The Author(s).
Références
J Immunother Cancer. 2020 May;8(1):
pubmed: 32457124
Int J Mol Sci. 2019 Oct 17;20(20):
pubmed: 31627272
Medicine (Baltimore). 2019 Feb;98(8):e14663
pubmed: 30813210
Immunotherapy. 2017 Jun;9(7):607-616
pubmed: 28595517
Cancer Discov. 2012 May;2(5):401-4
pubmed: 22588877
Ann Oncol. 2016 Jan;27(1):147-53
pubmed: 26483045
Clin Cancer Res. 2016 Jul 15;22(14):3425-3431
pubmed: 27208063
JAMA Oncol. 2019 Oct 01;5(10):1431-1438
pubmed: 31318392
Mol Cancer Ther. 2017 Jul;16(7):1203-1211
pubmed: 28679835
Immune Netw. 2014 Dec;14(6):265-76
pubmed: 25550693
Mol Cancer. 2021 Jan 7;20(1):11
pubmed: 33413365
Signal Transduct Target Ther. 2021 Feb 20;6(1):72
pubmed: 33608497
Lancet. 2015 Mar 28;385(9974):1206-18
pubmed: 25479696
Clin Cancer Res. 2017 Jun 15;23(12):2934-2941
pubmed: 28325750
Front Oncol. 2021 Apr 15;11:600238
pubmed: 33937019
CA Cancer J Clin. 2021 May;71(3):209-249
pubmed: 33538338
Oncotarget. 2016 Apr 12;7(15):19738-47
pubmed: 26918451
Cancer Cell Int. 2019 Mar 11;19:55
pubmed: 30911286
Clin Cancer Res. 2017 Sep 1;23(17):5202-5209
pubmed: 28539467
CA Cancer J Clin. 2021 Jan;71(1):7-33
pubmed: 33433946
Eur J Cancer. 2020 Jul;133:74-85
pubmed: 32447027
Mol Cancer Ther. 2015 Apr;14(4):847-56
pubmed: 25695955
J Immunother Cancer. 2019 Mar 8;7(1):65
pubmed: 30850021
Sci Rep. 2021 Apr 6;11(1):7550
pubmed: 33824367
Science. 2018 Oct 12;362(6411):
pubmed: 30309915
JAMA Oncol. 2018 May 10;4(5):e180013
pubmed: 29543932
Hum Pathol. 2017 Aug;66:79-85
pubmed: 28600225
Cancer J. 2017 Jan/Feb;23(1):10-22
pubmed: 28114250
Pathol Res Pract. 2020 Mar;216(3):152736
pubmed: 31757662
J Clin Med. 2018 Jul 10;7(7):
pubmed: 29996538
Genes Chromosomes Cancer. 2021 May;60(5):373-384
pubmed: 33341987
Hepatobiliary Pancreat Dis Int. 2018 Apr;17(2):95-100
pubmed: 29576277