Communication between EMT and PD-L1 signaling: New insights into tumor immune evasion
Abstract
Immune checkpoint blockage has been considered a breakthrough in cancer treatment, achieving encouraging anti-tumor effects in some advanced solid malignancies. However, low response rate and therapeutic resistance represent significant challenges in this field. In addition to its typical role in embryonic development and tissue fibrosis, epithelial-mesenchymal transition (EMT) plays a pivotal role in tumor immunosuppression and immune evasion. Previous studies revealed that EMT is associated with activation of different immune checkpoint molecules, including PD-L1. EMT-induced immune escape promotes cancer progression and may also provide a platform for discovery of novel therapeutic approaches and predictive biomarkers for checkpoint inhibitor therapeutic response. Here, we summarize recent findings focused on EMT-induced immune suppression and evasion in the tumor microenvironment (TME). EMT transcription factors (EMT-TFs), immune cells, cell plasticity and their regulatory role in the immune response are thoroughly reviewed. Bidirectional regulation between EMT and PD-L1 signaling is discussed in terms of cancer immune escape and possible combined therapies. Additionally, we investigated the value of preclinical or clinical trials using EMT targeted therapy combined with PD-L1 inhibitors. This review may help to further understand the role of EMT and PD-L1 signaling in cancer immune evasion. Meanwhile, additional molecular mechanistic studies and clinical trials are urgently needed.
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EMT confers increased cancer cell expression of PD-L1, the ligand for PD-1 on CD8+ T cells.
“EMT also confers increased cancer cell expression of PD-L1, the ligand for the immune-inhibitory PD-1 receptor on CD8+ T lymphocytes141,146.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [146]
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TGFβ biology in cancer progression and immunotherapy
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- Authors
- Jiang, Y., & Zhan, H.
- Affiliations
- Shandong University (CN)
- Corresponding author
- Zhan, Hanxiang
- Venue
- Cancer Letters
- Publisher
- Elsevier BV
- Published
- 2020-01
- Volume
- 468
- Pages
- 72-81
- ISSN
- 0304-3835 (ISSN-L)
- OpenAlex
- W2979519501
- Cited by
- 319
- References
- 125
- Citations by year
- 2026: 23 · 2025: 45 · 2024: 53 · 2023: 50 · 2022: 66 · 2021: 58 · 2020: 23 · 2019: 1
- FWCI
- 3.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Cancer Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81702365, 81800039, 81972274)
- Shandong Provincial Natural Science Foundation, China (ZR2017MH090)
- China Scholarship Council (CSC. 201806225020)
- Shandong provincial scholarship for Non-educational system
- 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
- epithelial-mesenchymal transition, tumor immune evasion, tumor microenvironment, immune checkpoint inhibitors, EMT transcription factors, cellular plasticity, immune cell regulation, predictive biomarkers, combination therapy
- MeSH terms
- Antineoplastic Agents, Immunological, Antineoplastic Combined Chemotherapy Protocols, Drug Synergism, Humans, Neoplasms, Signal Transduction, Drug Resistance, Neoplasm, Tumor Escape, Cell Line, Tumor, Epithelial-Mesenchymal Transition, Tumor Microenvironment, B7-H1 Antigen, Programmed Cell Death 1 Receptor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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