-
Something wrong with this record ?
Abrogation of IFN-γ Signaling May not Worsen Sensitivity to PD-1/PD-L1 Blockade
J. Vackova, A. Piatakova, I. Polakova, M. Smahel,
Language English Country Switzerland
Document type Journal Article
Grant support
988218
Grantová Agentura, Univerzita Karlova
LQ1604
Ministerstvo Školství, Mládeže a Tělovýchovy
LM2018126
Ministerstvo Školství, Mládeže a Tělovýchovy
CZ.1.05/1.1.00/02.0109
European Regional Development Fund
CZ.1.05/2.1.00/19.0400
European Regional Development Fund
CZ.02.1.01/0.0/0.0/16_019/0000785
European Regional Development Fund
CZ.1.05/2.1.00/19.0395
European Regional Development Fund
NLK
Free Medical Journals
from 2000
Freely Accessible Science Journals
from 2000
PubMed Central
from 2007
Europe PubMed Central
from 2007
ProQuest Central
from 2000-03-01
Open Access Digital Library
from 2000-01-01
Open Access Digital Library
from 2007-01-01
Health & Medicine (ProQuest)
from 2000-03-01
ROAD: Directory of Open Access Scholarly Resources
from 2000
PubMed
32155707
DOI
10.3390/ijms21051806
Knihovny.cz E-resources
- MeSH
- B7-H1 Antigen antagonists & inhibitors MeSH
- Programmed Cell Death 1 Receptor antagonists & inhibitors MeSH
- Neoplasms, Experimental drug therapy immunology metabolism pathology MeSH
- Immunotherapy MeSH
- Interferon-gamma antagonists & inhibitors MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Tumor Cells, Cultured MeSH
- Antineoplastic Agents, Immunological pharmacology MeSH
- Cell Line, Transformed drug effects immunology metabolism pathology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) blockade is a promising therapy for various cancer types, but most patients are still resistant. Therefore, a larger number of predictive biomarkers is necessary. In this study, we assessed whether a loss-of-function mutation of the interferon (IFN)-γ receptor 1 (IFNGR1) in tumor cells can interfere with anti-PD-L1 therapy. For this purpose, we used the mouse oncogenic TC-1 cell line expressing PD-L1 and major histocompatibility complex class I (MHC-I) molecules and its TC-1/A9 clone with reversibly downregulated PD-L1 and MHC-I expression. Using the CRISPR/Cas9 system, we generated cells with deactivated IFNGR1 (TC-1/dIfngr1 and TC-1/A9/dIfngr1). In tumors, IFNGR1 deactivation did not lead to PD-L1 or MHC-I reduction on tumor cells. From potential inducers, mainly IFN-α and IFN-β enhanced PD-L1 and MHC-I expression on TC-1/dIfngr1 and TC-1/A9/dIfngr1 cells in vitro. Neutralization of the IFN-α/IFN-β receptor confirmed the effect of these cytokines in vivo. Combined immunotherapy with PD-L1 blockade and DNA vaccination showed that IFNGR1 deactivation did not reduce tumor sensitivity to anti-PD-L1. Thus, the impairment of IFN-γ signaling may not be sufficient for PD-L1 and MHC-I reduction on tumor cells and resistance to PD-L1 blockade, and thus should not be used as a single predictive marker for anti-PD-1/PD-L1 cancer therapy.
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc20028401
- 003
- CZ-PrNML
- 005
- 20210114153745.0
- 007
- ta
- 008
- 210105s2020 sz f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.3390/ijms21051806 $2 doi
- 035 __
- $a (PubMed)32155707
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a sz
- 100 1_
- $a Vackova, Julie $u Department of Genetics and Microbiology, Faculty of Science, Charles University, BIOCEV, 252 50 Vestec, Czech Republic. Department of Cell Biology, Faculty of Science, Charles University, BIOCEV, 252 50 Vestec, Czech Republic.
- 245 10
- $a Abrogation of IFN-γ Signaling May not Worsen Sensitivity to PD-1/PD-L1 Blockade / $c J. Vackova, A. Piatakova, I. Polakova, M. Smahel,
- 520 9_
- $a Programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) blockade is a promising therapy for various cancer types, but most patients are still resistant. Therefore, a larger number of predictive biomarkers is necessary. In this study, we assessed whether a loss-of-function mutation of the interferon (IFN)-γ receptor 1 (IFNGR1) in tumor cells can interfere with anti-PD-L1 therapy. For this purpose, we used the mouse oncogenic TC-1 cell line expressing PD-L1 and major histocompatibility complex class I (MHC-I) molecules and its TC-1/A9 clone with reversibly downregulated PD-L1 and MHC-I expression. Using the CRISPR/Cas9 system, we generated cells with deactivated IFNGR1 (TC-1/dIfngr1 and TC-1/A9/dIfngr1). In tumors, IFNGR1 deactivation did not lead to PD-L1 or MHC-I reduction on tumor cells. From potential inducers, mainly IFN-α and IFN-β enhanced PD-L1 and MHC-I expression on TC-1/dIfngr1 and TC-1/A9/dIfngr1 cells in vitro. Neutralization of the IFN-α/IFN-β receptor confirmed the effect of these cytokines in vivo. Combined immunotherapy with PD-L1 blockade and DNA vaccination showed that IFNGR1 deactivation did not reduce tumor sensitivity to anti-PD-L1. Thus, the impairment of IFN-γ signaling may not be sufficient for PD-L1 and MHC-I reduction on tumor cells and resistance to PD-L1 blockade, and thus should not be used as a single predictive marker for anti-PD-1/PD-L1 cancer therapy.
- 650 _2
- $a zvířata $7 D000818
- 650 _2
- $a protinádorové látky imunologicky aktivní $x farmakologie $7 D000074322
- 650 _2
- $a antigeny CD274 $x antagonisté a inhibitory $7 D060890
- 650 _2
- $a transformované buněčné linie $x účinky léků $x imunologie $x metabolismus $x patologie $7 D002461
- 650 _2
- $a ženské pohlaví $7 D005260
- 650 _2
- $a imunoterapie $7 D007167
- 650 _2
- $a interferon gama $x antagonisté a inhibitory $7 D007371
- 650 _2
- $a myši $7 D051379
- 650 _2
- $a myši inbrední C57BL $7 D008810
- 650 _2
- $a experimentální nádory $x farmakoterapie $x imunologie $x metabolismus $x patologie $7 D009374
- 650 _2
- $a antigeny CD279 $x antagonisté a inhibitory $7 D061026
- 650 _2
- $a nádorové buňky kultivované $7 D014407
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Piatakova, Adrianna $u Department of Genetics and Microbiology, Faculty of Science, Charles University, BIOCEV, 252 50 Vestec, Czech Republic.
- 700 1_
- $a Polakova, Ingrid $u Department of Genetics and Microbiology, Faculty of Science, Charles University, BIOCEV, 252 50 Vestec, Czech Republic.
- 700 1_
- $a Smahel, Michal $u Department of Genetics and Microbiology, Faculty of Science, Charles University, BIOCEV, 252 50 Vestec, Czech Republic.
- 773 0_
- $w MED00176142 $t International journal of molecular sciences $x 1422-0067 $g Roč. 21, č. 5 (2020)
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/32155707 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20210105 $b ABA008
- 991 __
- $a 20210114153742 $b ABA008
- 999 __
- $a ok $b bmc $g 1608736 $s 1119581
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2020 $b 21 $c 5 $e 20200306 $i 1422-0067 $m International journal of molecular sciences $n Int J Mol Sci $x MED00176142
- GRA __
- $a 988218 $p Grantová Agentura, Univerzita Karlova
- GRA __
- $a LQ1604 $p Ministerstvo Školství, Mládeže a Tělovýchovy
- GRA __
- $a LM2018126 $p Ministerstvo Školství, Mládeže a Tělovýchovy
- GRA __
- $a CZ.1.05/1.1.00/02.0109 $p European Regional Development Fund
- GRA __
- $a CZ.1.05/2.1.00/19.0400 $p European Regional Development Fund
- GRA __
- $a CZ.02.1.01/0.0/0.0/16_019/0000785 $p European Regional Development Fund
- GRA __
- $a CZ.1.05/2.1.00/19.0395 $p European Regional Development Fund
- LZP __
- $a Pubmed-20210105