Scaffold-Based (Matrigel™) 3D Culture Technique of Glioblastoma Recovers a Patient-like Immunosuppressive Phenotype.
GBM
brain cancer
next-generation sequencing
single-cell RNA sequencing
tumor organoids
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
14 07 2023
14 07 2023
Historique:
received:
02
06
2023
revised:
07
07
2023
accepted:
11
07
2023
medline:
31
7
2023
pubmed:
29
7
2023
entrez:
29
7
2023
Statut:
epublish
Résumé
Conventional 2D cultures are commonly used in cancer research though they come with limitations such as the lack of microenvironment or reduced cell heterogeneity. In this study, we investigated in what respect a scaffold-based (Matrigel™) 3D culture technique can ameliorate the limitations of 2D cultures. NGS-based bulk and single-cell sequencing of matched pairs of 2D and 3D models showed an altered transcription of key immune regulatory genes in around 36% of 3D models, indicating the reoccurrence of an immune suppressive phenotype. Changes included the presentation of different HLA surface molecules as well as cellular stressors. We also investigated the 3D tumor organoids in a co-culture setting with tumor-infiltrating lymphocytes (TILs). Of note, lymphocyte-mediated cell killing appeared less effective in clearing 3D models than their 2D counterparts. IFN-γ release, as well as live cell staining and proliferation analysis, pointed toward an elevated resistance of 3D models. In conclusion, we found that the scaffold-based (Matrigel™) 3D culture technique affects the transcriptional profile in a subset of GBM models. Thus, these models allow for depicting clinically relevant aspects of tumor-immune interaction, with the potential to explore immunotherapeutic approaches in an easily accessible in vitro system.
Identifiants
pubmed: 37508520
pii: cells12141856
doi: 10.3390/cells12141856
pmc: PMC10378658
pii:
doi:
Substances chimiques
Immunosuppressive Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Références
J Immunol. 2003 Aug 1;171(3):1376-84
pubmed: 12874228
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Cancer Res. 2016 Apr 15;76(8):2465-77
pubmed: 26896279
Cancer Cell. 2010 Jan 19;17(1):98-110
pubmed: 20129251
Cancer Immunol Res. 2020 Sep;8(9):1163-1179
pubmed: 32665263
Nat Protoc. 2014 Oct;9(10):2329-40
pubmed: 25188634
Genome Biol. 2014;15(12):550
pubmed: 25516281
Curr Opin Immunol. 2018 Apr;51:55-61
pubmed: 29525346
STAR Protoc. 2020 Jun 19;1(1):
pubmed: 33103125
Cell. 2019 Aug 8;178(4):835-849.e21
pubmed: 31327527
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Nat Rev Mater. 2019 Oct;4(10):651-668
pubmed: 32647587
Trends Neurosci. 1997 Oct;20(10):471-7
pubmed: 9347615
Front Toxicol. 2021 May 04;3:656254
pubmed: 35295158
Oncotarget. 2017 Jan 31;8(5):8250-8263
pubmed: 28030813
Cell. 2017 Nov 30;171(6):1259-1271.e11
pubmed: 29107330
BMC Cancer. 2022 Aug 3;22(1):844
pubmed: 35922758
Bioinformatics. 2020 Apr 1;36(7):2311-2313
pubmed: 31764967
CA Cancer J Clin. 2020 Jul;70(4):299-312
pubmed: 32478924
Nat Rev Cancer. 2020 Jan;20(1):12-25
pubmed: 31806885
Bioinformatics. 2018 Apr 1;34(7):1208-1214
pubmed: 29186351
Cell. 2021 Jun 24;184(13):3573-3587.e29
pubmed: 34062119
J Immunother. 2003 Jul-Aug;26(4):332-42
pubmed: 12843795
Cell Rep. 2019 Mar 19;26(12):3203-3211.e5
pubmed: 30893594
Front Immunol. 2022 Jul 27;13:964898
pubmed: 35967394
Nature. 2018 Mar 22;555(7697):469-474
pubmed: 29539639
Biostatistics. 2017 Apr 1;18(2):275-294
pubmed: 27756721
Cells. 2022 Dec 20;12(1):
pubmed: 36611806
Expert Rev Mol Med. 2021 Dec 02;23:e20
pubmed: 34852856
J Vis Exp. 2022 Aug 25;(186):
pubmed: 36094291
Sci Rep. 2022 May 4;12(1):7235
pubmed: 35508592
Acta Neuropathol Commun. 2020 Aug 5;8(1):124
pubmed: 32758285
Cancer Res. 2020 Mar 15;80(6):1258-1267
pubmed: 31767628
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Ann Oncol. 2023 Mar;34(3):300-314
pubmed: 36494005
Neuro Oncol. 2019 Nov 1;21(Suppl 5):v1-v100
pubmed: 31675094
Nat Protoc. 2006;1(3):1458-61
pubmed: 17406435
Front Immunol. 2020 Oct 14;11:585616
pubmed: 33154756
PLoS One. 2019 Jan 24;14(1):e0211078
pubmed: 30677075
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Neoplasia. 2015 Jan;17(1):1-15
pubmed: 25622895
Neuro Oncol. 2021 Aug 2;23(8):1231-1251
pubmed: 34185076
Cancer Cell. 2021 Jun 14;39(6):779-792.e11
pubmed: 34087162
Nat Methods. 2015 Apr;12(4):357-60
pubmed: 25751142
Pharmaceutics. 2023 Jun 09;15(6):
pubmed: 37376148
Neoplasia. 2018 Jul;20(7):710-720
pubmed: 29852323
Cell Rep. 2019 Mar 26;26(13):3672-3683.e7
pubmed: 30917320
Int J Mol Sci. 2022 Nov 23;23(23):
pubmed: 36498949
JAMA. 2017 Dec 19;318(23):2306-2316
pubmed: 29260225
Methods Mol Biol. 2023;2572:117-127
pubmed: 36161412
Int J Mol Sci. 2022 May 23;23(10):
pubmed: 35628668
N Engl J Med. 2005 Mar 10;352(10):987-96
pubmed: 15758009
Bioinformatics. 2017 Dec 15;33(24):3982-3984
pubmed: 28961746