The immune checkpoint ligand PD-L1 is upregulated in EMT-activated human breast cancer cells by a mechanism involving ZEB-1 and miR-200
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PD-L1 expression and regulation by mesenchymal tumor cells remain largely undefined. Here, we report that among different EMT-activated MCF7 human breast cancer cell clones, PD-L1 was differentially upregulated in MCF7 sh-WISP2, MCF7-1001/2101, and MDA-MB-231 cells but not in MCF7 SNAI1 and MCF7 SNAI1-6SA cells. Mechanistic investigations revealed that siRNA silencing of ZEB-1, but not SNAI1, TWIST, or SLUG and overexpression of miR200 family members in MCF7 sh-WISP2 cells strongly decreased PD-L1 expression. Thus, we propose that PD-L1 expression in EMT-activated breast cancer cells depends on the EMT-TF involved in EMT activation. Interestingly, siRNA-mediated targeting of PD-L1 or antibody-mediated PD-L1 block restored the susceptibility of highly resistant MCF7 sh-WISP2 and MCF7-2101 cells to CTL-mediated killing. Additionally, these results provide a novel preclinical rationale to explore EMT inhibitors as adjuvants to boost immunotherapeutic responses in subgroups of patients in whom malignant progression is driven by different EMT-TFs.
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EMT of carcinoma cells in response to increased TGF-β signaling is accompanied, in some tumors, by increased PD-L1 expression.
“Notably, EMT of carcinoma cells in response to increased TGF-β signaling is accompanied, in some tumors, by increased PD-L1 expression37,355,356.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [356]
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- Authors
- Noman, M. Z., Janji, B., Abdou, A., Hasmim, M., Terry, S., Tan, T. Z., Mami-Chouaib, F., Thiery, J. P., & Chouaib, S.
- Affiliations
- Université Paris-Sud (FR)
- Luxembourg Institute of Health (LU)
- INSERM UMR 1186, Integrative Tumor Immunology and Genetic Oncology, Gustave Roussy, EPHE, Fac. de médecine - Univ. Paris-Sud, Université Paris-Saclay, Villejuif, France
- National University of Singapore (SG)
- Venue
- OncoImmunology
- Publisher
- Informa UK Limited
- Published
- 2017-01-02
- Volume
- 6
- Issue
- 1
- Pages
- e1263412
- ISSN
- 2162-4011 (ISSN-L)
- 2162-402X
- PMC
- PMC5283623
- OpenAlex
- W2581279204
- Cited by
- 253
- References
- 20
- Citations by year
- 2026: 13 · 2025: 15 · 2024: 22 · 2023: 16 · 2022: 41 · 2021: 41 · 2020: 47 · 2019: 20 · 2018: 26 · 2017: 12
- FWCI
- 12.66
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- OncoImmunology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Fonds De La Recherche Scientifique - FNRS (7.4664.15)
- Ligue Contre le Cancer
- Institut National Du Cancer (PLBIO15‐266)
- Groupement des Entreprises Françaises dans la lutte contre le Cancer
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- PD-L1, epithelial-mesenchymal transition, ZEB1, miR-200 family, breast cancer, immune checkpoint, WISP2, SNAI1, Twist, Slug, CTL-mediated killing, EMT transcription factors, EMT inhibitors, cancer immunotherapy
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