Transcriptomic adaptation of the cold versus hot triple-negative breast tumor immune microenvironment to PD-L1 blockade
- Author
- Robbe Salembier (UGent) , Caro De Haes (UGent) , Bo Wylin (UGent) , Kristel Demeyere (UGent) , Steven Van Laere, Nicolaas Van Renne (UGent) , Christos Sotiriou, Evelyne Meyer (UGent) and Jonas Steenbrugge (UGent)
- Organization
- Abstract
- A limited subset of triple-negative breast cancer (TNBC) patients benefit from immune checkpoint blockade (ICB) such as anti-programmed death (PD)-ligand (L)1. The vastly different ‘cold’ versus ‘hot’ TNBC tumor immune microenvironment (TIME) plays a key role in this heterogeneous ICB efficacy. Here, a 4T1-cold- and 4T1-hot-based mouse TNBC model was used to identify differential TIME adaptation mechanisms to anti-PD-L1 blockade. Despite the absence of tumor growth reduction, anti-PD-L1-treated 4T1-cold primary tumors showed increased expression of genes associated with anti-tumor immunity and inflammatory responses, shifting their ‘cold’ TIME to a ‘hot’ state with downregulation of cellular mitosis and tumor progression hallmarks. In contrast, anti-PD-L1 treatment upregulated tumor progression hallmarks in 4T1-hot tumors. Using a public single cell RNA-sequencing atlas from human TNBC patient tumors, we annotated significantly upregulated genes in 4T1-cold and 4T1-hot primary tumors upon anti-PD-L1 treatment to CXCL10+ tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), respectively, and set up a specific gene signature for both populations. Although the CXCL10+ TAM signature associated with significantly increased distant metastasis-free survival (DMFS) in human TNBC patients, the high PD-L1 expression of these TAMs highlights its potential immunosuppressive properties in the TNBC TIME. The CAF signature associated with significantly decreased DMFS in human TNBC patients and decreased progression-free survival (PFS) upon anti-PD-L1 treatment in other cancer types. Collectively, our mouse TNBC models identified relevant TIME-specific adaptation mechanisms to ICB for future translational studies.
- Keywords
- TNBC, Cancer, ICB, PD-L1, immune checkpoint blockade, triple-negative breast cancer
Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01JV1P27DVYAFMCD5S23Q9EB4D
- MLA
- Salembier, Robbe, et al. “Transcriptomic Adaptation of the Cold versus Hot Triple-Negative Breast Tumor Immune Microenvironment to PD-L1 Blockade.” Immune Niches in Cancer & Inflammation Conference 2025, Abstracts, 2025.
- APA
- Salembier, R., De Haes, C., Wylin, B., Demeyere, K., Van Laere, S., Van Renne, N., … Steenbrugge, J. (2025). Transcriptomic adaptation of the cold versus hot triple-negative breast tumor immune microenvironment to PD-L1 blockade. Immune Niches in Cancer & Inflammation Conference 2025, Abstracts. Presented at the Immune Niches in Cancer & Inflammation Conference 2025, Bruges, Belgium.
- Chicago author-date
- Salembier, Robbe, Caro De Haes, Bo Wylin, Kristel Demeyere, Steven Van Laere, Nicolaas Van Renne, Christos Sotiriou, Evelyne Meyer, and Jonas Steenbrugge. 2025. “Transcriptomic Adaptation of the Cold versus Hot Triple-Negative Breast Tumor Immune Microenvironment to PD-L1 Blockade.” In Immune Niches in Cancer & Inflammation Conference 2025, Abstracts.
- Chicago author-date (all authors)
- Salembier, Robbe, Caro De Haes, Bo Wylin, Kristel Demeyere, Steven Van Laere, Nicolaas Van Renne, Christos Sotiriou, Evelyne Meyer, and Jonas Steenbrugge. 2025. “Transcriptomic Adaptation of the Cold versus Hot Triple-Negative Breast Tumor Immune Microenvironment to PD-L1 Blockade.” In Immune Niches in Cancer & Inflammation Conference 2025, Abstracts.
- Vancouver
- 1.Salembier R, De Haes C, Wylin B, Demeyere K, Van Laere S, Van Renne N, et al. Transcriptomic adaptation of the cold versus hot triple-negative breast tumor immune microenvironment to PD-L1 blockade. In: Immune Niches in Cancer & Inflammation Conference 2025, Abstracts. 2025.
- IEEE
- [1]R. Salembier et al., “Transcriptomic adaptation of the cold versus hot triple-negative breast tumor immune microenvironment to PD-L1 blockade,” in Immune Niches in Cancer & Inflammation Conference 2025, Abstracts, Bruges, Belgium, 2025.
@inproceedings{01JV1P27DVYAFMCD5S23Q9EB4D,
abstract = {{A limited subset of triple-negative breast cancer (TNBC) patients benefit from immune checkpoint blockade (ICB) such as anti-programmed death (PD)-ligand (L)1. The vastly different ‘cold’ versus ‘hot’ TNBC tumor immune microenvironment (TIME) plays a key role in this heterogeneous ICB efficacy.
Here, a 4T1-cold- and 4T1-hot-based mouse TNBC model was used to identify differential TIME adaptation mechanisms to anti-PD-L1 blockade. Despite the absence of tumor growth reduction, anti-PD-L1-treated 4T1-cold primary tumors showed increased expression of genes associated with anti-tumor immunity and inflammatory responses, shifting their ‘cold’ TIME to a ‘hot’ state with downregulation of cellular mitosis and tumor progression hallmarks. In contrast, anti-PD-L1 treatment upregulated tumor progression hallmarks in 4T1-hot tumors. Using a public single cell RNA-sequencing atlas from human TNBC patient tumors, we annotated significantly upregulated genes in 4T1-cold and 4T1-hot primary tumors upon anti-PD-L1 treatment to CXCL10+ tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), respectively, and set up a specific gene signature for both populations. Although the CXCL10+ TAM signature associated with significantly increased distant metastasis-free survival (DMFS) in human TNBC patients, the high PD-L1 expression of these TAMs highlights its potential immunosuppressive properties in the TNBC TIME. The CAF signature associated with significantly decreased DMFS in human TNBC patients and decreased progression-free survival (PFS) upon anti-PD-L1 treatment in other cancer types. Collectively, our mouse TNBC models identified relevant TIME-specific adaptation mechanisms to ICB for future translational studies.}},
author = {{Salembier, Robbe and De Haes, Caro and Wylin, Bo and Demeyere, Kristel and Van Laere, Steven and Van Renne, Nicolaas and Sotiriou, Christos and Meyer, Evelyne and Steenbrugge, Jonas}},
booktitle = {{Immune Niches in Cancer & Inflammation Conference 2025, Abstracts}},
keywords = {{TNBC,Cancer,ICB,PD-L1,immune checkpoint blockade,triple-negative breast cancer}},
language = {{eng}},
location = {{Bruges, Belgium}},
title = {{Transcriptomic adaptation of the cold versus hot triple-negative breast tumor immune microenvironment to PD-L1 blockade}},
url = {{https://www.vibconferences.be/events/immune-niches-in-cancer-inflammation#program}},
year = {{2025}},
}