Immune Cell Profiling of Peripheral Blood as Signature for Response During Checkpoint Inhibition Across Cancer Types.
PBMCs
clinical outcome
immune checkpoint inhibition
immune signature
prediction
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2021
2021
Historique:
received:
01
05
2020
accepted:
04
03
2021
entrez:
12
4
2021
pubmed:
13
4
2021
medline:
13
4
2021
Statut:
epublish
Résumé
Despite encouraging results with immune checkpoint inhibition (ICI), a large fraction of cancer patients still does not achieve clinical benefit. Finding predictive markers in the complexity of the tumor microenvironment is a challenging task and often requires invasive procedures. In our study, we looked for putative variables related to treatment benefit among immune cells in peripheral blood across different tumor types treated with ICIs. For that, we included 33 patients with different solid tumors referred to our clinical unit for ICI. Peripheral blood mononuclear cells were isolated at baseline, 6 and 20 weeks after treatment start. Characterization of immune cells was carried out by multi-color flow cytometry. Response to treatment was assessed radiologically by RECIST 1.1. Clinical outcome correlated with a shift towards an effector-like T cell phenotype, PD-1 expression by CD8+T cells, low levels of myeloid-derived suppressor cells and classical monocytes. Dendritic cells seemed also to play a role in terms of survival. From these findings, we hypothesized that patients responding to ICI had already at baseline an immune profile, here called 'favorable immune periphery', providing a higher chance of benefitting from ICI. We elaborated an index comprising cell types mentioned above. This signature correlated positively with the likelihood of benefiting from the treatment and ultimately with longer survival. Our study illustrates that patients responding to ICI seem to have a pre-existing immune profile in peripheral blood that favors good outcome. Exploring this signature can help to identify patients likely to achieve benefit from ICI.
Identifiants
pubmed: 33842304
doi: 10.3389/fonc.2021.558248
pmc: PMC8027233
doi:
Types de publication
Journal Article
Langues
eng
Pagination
558248Informations de copyright
Copyright © 2021 Araujo B. de Lima, Hansen, Spanggaard, Rohrberg, Reker Hadrup, Lassen and Svane.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Clin Cancer Res. 2008 Aug 15;14(16):5242-9
pubmed: 18698043
Nat Med. 2016 Apr;22(4):433-8
pubmed: 26901407
N Engl J Med. 2010 Aug 19;363(8):711-23
pubmed: 20525992
J Clin Oncol. 2015 Jun 10;33(17):1889-94
pubmed: 25667295
Cell. 2015 Jan 15;160(1-2):48-61
pubmed: 25594174
JCI Insight. 2016 Apr 21;1(5):
pubmed: 27182555
Cancer Immunol Res. 2014 Aug;2(8):812-21
pubmed: 24844912
N Engl J Med. 2017 Dec 21;377(25):2500-2501
pubmed: 29262275
Immunology. 1986 Apr;57(4):595-603
pubmed: 3007336
Cancer. 2008 Jan 15;112(2):407-15
pubmed: 18058809
Science. 2016 May 6;352(6286):658-60
pubmed: 27151852
Eur J Cancer. 2017 Mar;73:61-70
pubmed: 28167454
Cancer Immunol Immunother. 2018 Dec;67(12):1845-1851
pubmed: 30218171
Cell. 2017 Nov 2;171(4):934-949.e16
pubmed: 29033130
Science. 2015 Apr 3;348(6230):124-8
pubmed: 25765070
Science. 2015 Oct 9;350(6257):207-211
pubmed: 26359337
Lancet Oncol. 2016 Dec;17(12):e542-e551
pubmed: 27924752
Nat Med. 2019 Aug;25(8):1251-1259
pubmed: 31359002
Adv Cancer Res. 2015;128:95-139
pubmed: 26216631
Int Immunol. 2009 Sep;21(9):1065-77
pubmed: 19651643
J Immunother Cancer. 2016 Jun 21;4:38
pubmed: 27330811
J Transl Med. 2012 Oct 03;10:205
pubmed: 23034130
Nat Med. 2015 Aug;21(8):938-945
pubmed: 26193342
Eur J Immunol. 1999 Sep;29(9):2769-78
pubmed: 10508251
J Immunother. 2012 Nov-Dec;35(9):702-10
pubmed: 23090079
Nat Med. 2018 Feb;24(2):144-153
pubmed: 29309059
J Clin Invest. 2014 May;124(5):2246-59
pubmed: 24667641
Lancet Oncol. 2016 Nov;17(11):1558-1568
pubmed: 27622997
Clin Immunol. 2011 Jan;138(1):85-96
pubmed: 21056008
JCI Insight. 2019 Apr 4;4(7):
pubmed: 30944253
N Engl J Med. 2005 Dec 22;353(25):2654-66
pubmed: 16371631
Blood. 2001 Jul 1;98(1):140-5
pubmed: 11418473
Clin Cancer Res. 2015 Dec 15;21(24):5453-9
pubmed: 26289067
Cancer Lett. 2019 Aug 10;457:168-179
pubmed: 31078738
Int Immunol. 2018 Feb 3;30(1):13-22
pubmed: 29294043
Front Immunol. 2012 Feb 23;3:21
pubmed: 22566905
Front Oncol. 2018 Jul 18;8:270
pubmed: 30073150
J Immunol. 2005 Dec 1;175(11):7746-54
pubmed: 16301685
Hepatobiliary Surg Nutr. 2018 Dec;7(6):481-483
pubmed: 30652094
Lancet Oncol. 2015 Mar;16(3):257-65
pubmed: 25704439
Cancer Immunol Immunother. 2014 Mar;63(3):247-57
pubmed: 24357148
Proc Natl Acad Sci U S A. 2017 May 9;114(19):4993-4998
pubmed: 28446615
J Exp Med. 1997 Nov 3;186(9):1407-18
pubmed: 9348298