Low-density lipoprotein balances T cell metabolism and enhances response to anti-PD-1 blockade in a HCT116 spheroid model.
CD154 (CD40L)
LDL (low-density lipoprotein)
PD-1
central memory (T) CM
cholesterol
immunotherapy
reactive oxygen species
spheroid model
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2023
2023
Historique:
received:
25
11
2022
accepted:
10
01
2023
entrez:
13
2
2023
pubmed:
14
2
2023
medline:
14
2
2023
Statut:
epublish
Résumé
The discovery of immune checkpoints and the development of their specific inhibitors was acclaimed as a major breakthrough in cancer therapy. However, only a limited patient cohort shows sufficient response to therapy. Hence, there is a need for identifying new checkpoints and predictive biomarkers with the objective of overcoming immune escape and resistance to treatment. Having been associated with both, treatment response and failure, LDL seems to be a double-edged sword in anti-PD1 immunotherapy. Being embedded into complex metabolic conditions, the impact of LDL on distinct immune cells has not been sufficiently addressed. Revealing the effects of LDL on T cell performance in tumor immunity may enable individual treatment adjustments in order to enhance the response to routinely administered immunotherapies in different patient populations. The object of this work was to investigate the effect of LDL on T cell activation and tumor immunity Experiments were performed with different LDL dosages (LDL The key points of our findings showed that LDL Further research needs to be conducted to fully understand the impact of LDL on T cells in tumor immunity and moreover, to also unravel LDL effects on other lymphocytes and myeloid cells for improving anti-PD-1 immunotherapy. The reason for improved response might be a resilient, less exhausted phenotype with balanced ROS levels.
Identifiants
pubmed: 36776340
doi: 10.3389/fonc.2023.1107484
pmc: PMC9911890
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1107484Informations de copyright
Copyright © 2023 Babl, Hofbauer, Matos, Voll, Menevse, Rechenmacher, Mair, Beckhove, Herr, Siska, Renner, Kreutz and Schnell.
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
J Virol. 2005 Apr;79(7):4510-3
pubmed: 15767451
Front Immunol. 2021 Mar 31;12:652687
pubmed: 33868291
Cancer Immunol Res. 2021 Feb;9(2):214-226
pubmed: 33303575
Cancer Treat Rev. 2015 May;41(5):431-40
pubmed: 25843228
Nature. 2016 Mar 31;531(7596):651-5
pubmed: 26982734
Immunol Cell Biol. 2019 Aug;97(7):636-646
pubmed: 31127964
Cancer Res. 1990 Dec 1;50(23):7450-6
pubmed: 1701343
PLoS Biol. 2021 Apr 26;19(4):e3001199
pubmed: 33901179
Nat Rev Mol Cell Biol. 2020 Apr;21(4):225-245
pubmed: 31848472
Cell Metab. 2016 Jan 12;23(1):63-76
pubmed: 26674251
Front Oncol. 2021 Mar 17;10:626912
pubmed: 33816214
J Hematol Oncol. 2021 Nov 6;14(1):187
pubmed: 34742349
Sci Immunol. 2020 Dec 11;5(54):
pubmed: 33310866
Front Immunol. 2019 Aug 07;10:1888
pubmed: 31440257
Oncotarget. 2017 May 29;8(37):61425-61439
pubmed: 28977875
Front Med (Lausanne). 2019 Jul 31;6:174
pubmed: 31417907
Clin Cancer Res. 2020 May 1;26(9):2257-2267
pubmed: 31932494
Mol Cancer. 2021 Nov 10;20(1):146
pubmed: 34758832
J Exp Med. 2006 Feb 20;203(2):401-12
pubmed: 16476765
Hum Vaccin Immunother. 2021 Jul 3;17(7):1930-1934
pubmed: 33427023
Mol Cells. 2019 Nov 30;42(11):747-754
pubmed: 31766832
Front Oncol. 2020 Aug 04;10:1262
pubmed: 32850383
Nutrients. 2020 Jul 07;12(7):
pubmed: 32645995
Front Immunol. 2017 Nov 27;8:1664
pubmed: 29230226
Oncotarget. 2018 Feb 7;9(17):13125-13138
pubmed: 29568345
Cancer Manag Res. 2021 May 18;13:4041-4053
pubmed: 34040444
Nat Chem Biol. 2015 Feb;11(2):141-7
pubmed: 25558972
JCI Insight. 2017 Apr 6;2(7):e90652
pubmed: 28405614
J Immunother Cancer. 2019 Oct 26;7(1):278
pubmed: 31655605
Curr Opin Immunol. 2017 Jun;46:14-22
pubmed: 28412583
Cancer Immunol Res. 2019 May;7(5):759-772
pubmed: 30890531
Sci Rep. 2021 Jul 28;11(1):15312
pubmed: 34321489
J Biol Chem. 2012 Dec 14;287(51):42664-74
pubmed: 23091059
Cancer Res. 2015 Sep 15;75(18):3800-11
pubmed: 26208901
Cancer Immunol Immunother. 2022 Jan;71(1):203-217
pubmed: 34091744
Immunity. 2010 Jan 29;32(1):104-15
pubmed: 20079666
J Immunother Cancer. 2020 Aug;8(2):
pubmed: 32817209
Nat Immunol. 2013 May;14(5):489-99
pubmed: 23563690
PLoS One. 2012;7(6):e38733
pubmed: 22723880
Cell Metab. 2019 Jul 2;30(1):143-156.e5
pubmed: 31031094
BMC Immunol. 2019 Aug 7;20(1):27
pubmed: 31390978
Immune Netw. 2018 Feb 22;18(1):e14
pubmed: 29503744
J Immunol. 2005 Sep 15;175(6):3656-62
pubmed: 16148110
PLoS One. 2013 May 21;8(5):e63746
pubmed: 23704936
Nat Rev Cardiol. 2020 Jul;17(7):387-401
pubmed: 32203286
Nat Immunol. 2021 Feb;22(2):205-215
pubmed: 33398183
Nutr Metab Cardiovasc Dis. 2022 Jul;32(7):1693-1702
pubmed: 35469729
Circulation. 2001 Nov 13;104(20):2395-400
pubmed: 11705814
PLoS One. 2011;6(7):e22560
pubmed: 21829468
Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3018-23
pubmed: 20133700
Nat Commun. 2019 Jan 30;10(1):498
pubmed: 30700717
Oncogene. 2019 Nov;38(48):7357-7365
pubmed: 31417180
Nat Commun. 2017 Nov 13;8(1):1447
pubmed: 29129918
J Immunol. 2016 Aug 15;197(4):1308-21
pubmed: 27402701
J Clin Invest. 2016 Sep 1;126(9):3236-46
pubmed: 27482882
J Immunol. 2011 Nov 1;187(9):4421-5
pubmed: 21949017
Biochem J. 1998 Mar 1;330 ( Pt 2):659-66
pubmed: 9480872
Front Immunol. 2020 Nov 30;11:586907
pubmed: 33329566
J Inflamm Res. 2022 Jan 08;15:141-152
pubmed: 35035226
Oncol Lett. 2020 Nov;20(5):176
pubmed: 32934743
Cell Death Discov. 2019 Dec 4;5:148
pubmed: 31815003
Mol Cancer. 2010 Mar 08;9:52
pubmed: 20211016
Biomolecules. 2022 May 18;12(5):
pubmed: 35625643
Front Immunol. 2022 Jan 17;12:785091
pubmed: 35111155
Immunity. 2016 May 17;44(5):1091-101
pubmed: 27192576
J Immunother. 2020 Jul/Aug;43(6):196-203
pubmed: 32404654
EMBO Mol Med. 2019 Jul;11(7):e10293
pubmed: 31273938
Cell Rep. 2019 Jun 4;27(10):2948-2961.e7
pubmed: 31167140
Ann N Y Acad Sci. 2012 Jul;1259:54-64
pubmed: 22758637
Protein Cell. 2020 Aug;11(8):549-564
pubmed: 32221812
Cell Metab. 2017 Jul 5;26(1):94-109
pubmed: 28683298
Exp Hematol. 2016 Sep;44(9):799-808
pubmed: 27423815
Curr Opin Immunol. 2022 Feb;74:18-24
pubmed: 34619457
Nanomedicine. 2018 Nov;14(8):2541-2550
pubmed: 30193815
Cell Metab. 2015 Apr 7;21(4):517-26
pubmed: 25863245
Genes Dis. 2018 Oct 18;5(4):302-303
pubmed: 30591930
J Immunother. 2020 Oct;43(8):236-243
pubmed: 32804915
J Infect Dis. 2021 Nov 16;224(9):1599-1604
pubmed: 33744939
Immunol Cell Biol. 2021 Mar;99(3):288-298
pubmed: 32940916
J Immunother Cancer. 2019 Nov 29;7(1):331
pubmed: 31783783