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Transcriptomic adaptation of the cold versus hot triple-negative breast tumor immune microenvironment to PD-L1 blockade

Author
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

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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}},
}