Transcriptomic heterogeneity of nine complementary mouse TNBC models based on their comparative in vitro and in vivo characterization
- Author
- Robbe Salembier (UGent) , Caro De Haes (UGent) , Bo Wylin (UGent) , Kristel Demeyere (UGent) , Steven Van Laere, Niek Sanders (UGent) , Evelyne Meyer (UGent) and Jonas Steenbrugge (UGent)
- Organization
- Abstract
- Triple-negative breast cancer (TNBC) represents up to 20% of all breast cancers and is the subtype with the worst outcome. To preclinically capture the remarkable tumor immune microenvironment (TIME) heterogeneity observed in TNBC patients, we characterized 9 complementary TNBC models, relying on the truly orthotopic (i.e. intraductal) inoculation of established mouse TNBC cell lines in syngeneic mouse trains, i.e. BALB/C for 4T1-hot, -cold, EMT6, D2A1 and 66cl4; C57BL/6 for Py230 and AT-3; FVB/N for MVT-1 and MET-1. Heterogeneity was already captured at the in vitro level, with cell lines showing vastly different growth kinetics, identifying EMT6 as the fastest- and PY230 and AT3 as the slowest-growing cell line. The differential in vitro cell growth was corroborated by nutrient uptake, cyto-/chemokine and associated hallmark expression in our generated single cell RNA-sequencing atlas of these mouse TNBC cell lines. The transcriptomic landscape of the primary tumors following in vivo inoculation showed a clear influence of the TIME with cellular metabolism switching from oxygen dependent metabolism to a glycolysis-based oxygen-independent metabolism and upregulated expression of MYC target genes. Based on the expression of immune-related gene sets the AT3- and D2A1-based model displayed the most prominent ‘cold’ TIME. Corroborating their presumed ‘hot’ TIME, 4T1-hot primary tumors showed increased gene expression related to IFN-α and -γ signaling, T-cell activation, T-cell exhaustion and antigen presentation compared to the 4T1-cold counterparts. These characterized mouse TNBC models are now explored to in-depth investigate the influence of TIME heterogeneity on (immuno)therapeutic efficacy in TNBC.
- Keywords
- TNBC, Oncology, Cancer, ICB, Immunecheckpoint blockade, Breast cancer
Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01JQX8TAYEV00TAV7YN4XZ4QVE
- MLA
- Salembier, Robbe, et al. “Transcriptomic Heterogeneity of Nine Complementary Mouse TNBC Models Based on Their Comparative in Vitro and in Vivo Characterization.” OncoPoint Symposium, 11th, Abstracts, 2025.
- APA
- Salembier, R., De Haes, C., Wylin, B., Demeyere, K., Van Laere, S., Sanders, N., … Steenbrugge, J. (2025). Transcriptomic heterogeneity of nine complementary mouse TNBC models based on their comparative in vitro and in vivo characterization. OncoPoint Symposium, 11th, Abstracts. Presented at the OncoPoint Symposium 2025, Sint-Pietersabdij Gent, Ghent, Belgium.
- Chicago author-date
- Salembier, Robbe, Caro De Haes, Bo Wylin, Kristel Demeyere, Steven Van Laere, Niek Sanders, Evelyne Meyer, and Jonas Steenbrugge. 2025. “Transcriptomic Heterogeneity of Nine Complementary Mouse TNBC Models Based on Their Comparative in Vitro and in Vivo Characterization.” In OncoPoint Symposium, 11th, Abstracts.
- Chicago author-date (all authors)
- Salembier, Robbe, Caro De Haes, Bo Wylin, Kristel Demeyere, Steven Van Laere, Niek Sanders, Evelyne Meyer, and Jonas Steenbrugge. 2025. “Transcriptomic Heterogeneity of Nine Complementary Mouse TNBC Models Based on Their Comparative in Vitro and in Vivo Characterization.” In OncoPoint Symposium, 11th, Abstracts.
- Vancouver
- 1.Salembier R, De Haes C, Wylin B, Demeyere K, Van Laere S, Sanders N, et al. Transcriptomic heterogeneity of nine complementary mouse TNBC models based on their comparative in vitro and in vivo characterization. In: OncoPoint Symposium, 11th, Abstracts. 2025.
- IEEE
- [1]R. Salembier et al., “Transcriptomic heterogeneity of nine complementary mouse TNBC models based on their comparative in vitro and in vivo characterization,” in OncoPoint Symposium, 11th, Abstracts, Sint-Pietersabdij Gent, Ghent, Belgium, 2025.
@inproceedings{01JQX8TAYEV00TAV7YN4XZ4QVE,
abstract = {{Triple-negative breast cancer (TNBC) represents up to 20% of all breast cancers and is the subtype with the worst outcome.
To preclinically capture the remarkable tumor immune microenvironment (TIME) heterogeneity observed in TNBC patients, we characterized 9 complementary TNBC models, relying on the truly orthotopic (i.e. intraductal) inoculation of established mouse TNBC cell lines in syngeneic mouse trains, i.e. BALB/C for 4T1-hot, -cold, EMT6, D2A1 and 66cl4; C57BL/6 for Py230 and AT-3; FVB/N for MVT-1 and MET-1. Heterogeneity was already captured at the in vitro level, with cell lines showing vastly different growth kinetics, identifying EMT6 as the fastest- and PY230 and AT3 as the slowest-growing cell line. The differential in vitro cell growth was corroborated by nutrient uptake, cyto-/chemokine and associated hallmark expression in our generated single cell RNA-sequencing atlas of these mouse TNBC cell lines. The transcriptomic landscape of the primary tumors following in vivo inoculation showed a clear influence of the TIME with cellular metabolism switching from oxygen dependent metabolism to a glycolysis-based oxygen-independent metabolism and upregulated expression of MYC target genes. Based on the expression of immune-related gene sets the AT3- and D2A1-based model displayed the most prominent ‘cold’ TIME. Corroborating their presumed ‘hot’ TIME, 4T1-hot primary tumors showed increased gene expression related to IFN-α and -γ signaling, T-cell activation, T-cell exhaustion and antigen presentation compared to the 4T1-cold counterparts.
These characterized mouse TNBC models are now explored to in-depth investigate the influence of TIME heterogeneity on (immuno)therapeutic efficacy in TNBC.}},
author = {{Salembier, Robbe and De Haes, Caro and Wylin, Bo and Demeyere, Kristel and Van Laere, Steven and Sanders, Niek and Meyer, Evelyne and Steenbrugge, Jonas}},
booktitle = {{OncoPoint Symposium, 11th, Abstracts}},
keywords = {{TNBC,Oncology,Cancer,ICB,Immunecheckpoint blockade,Breast cancer}},
language = {{eng}},
location = {{Sint-Pietersabdij Gent, Ghent, Belgium}},
title = {{Transcriptomic heterogeneity of nine complementary mouse TNBC models based on their comparative in vitro and in vivo characterization}},
url = {{https://www.crig.ugent.be/en/events/oncopoint-symposium-2025}},
year = {{2025}},
}