Chemotherapy enhances programmed cell death 1/ligand 1 expression via TGF-β induced epithelial mesenchymal transition in non-small cell lung cancer
書誌事項
- 公開日
- 2017-04
- 資源種別
- journal article
- DOI
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- 10.3892/or.2017.5894
- 公開者
- Spandidos Publications
この論文をさがす
説明
In cancer immunology, the programmed cell death 1-programmed cell death 1/ligand 1 (PD-1/PD-L1) pathway plays a major role. Anti-PD-1 and anti-PD-L1 antibodies provide reliable immunotherapy when given as treatment for various types of malignancy including lung cancer. PD-L1 expression in cancer cells has been reported to be a predictive factor for the therapeutic effects of immunotherapy. However, the mechanism of PD-L1 expression remains unclear. Another key process in cancer progression is epithelial-mesenchymal transition (EMT). In the present study, we investigated the mechanism of PD-L1 expression as well as changes in its expression during the EMT process in non-small cell lung cancer (NSCLC). In this study, A549 cells underwent EMT by treatment with TGF-β or chemotherapeutic agents and then PD-L1 expression was evaluated. The alterations of PD-L1 expression was also examined during the reverse EMT process; mesenchymal-epithelial transition (MET). The relationship between for PD-L1 expression and EMT status in clinical specimens with NSCLC after induction chemotherapy were analyzed by immunohistochemical staining. We found that PD-L1 expression was upregulated following TGF-β induction; in contrast, it was downregulated by TGF-β receptor-kinase inhibitors and the MET process. Furthermore, chemo-treatment increased TGF-β expression and enhances PD-L1 expression via autocrine TGF-β induced EMT. Analysis of clinical samples revealed a significant relationship between PD-L1 expression and EMT status (P0.05). In conclusion, our results suggest that PD-L1 expression is regulated by TGF-β induced EMT and enhanced by chemo-treatment via the chemo-induced TGF-β signaling. The anti-PD-1/PD-L1 blockade may provide more effective anticancer activities in combination with chemotherapy in NSCLC.
収録刊行物
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- Oncology Reports
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Oncology Reports 38 (4), 2277-2284, 2017-04
Spandidos Publications
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キーワード
- Male
- Epithelial-Mesenchymal Transition
- Programmed Cell Death 1 Receptor
- Receptor, Transforming Growth Factor-beta Type II
- Antineoplastic Agents
- Middle Aged
- Protein Serine-Threonine Kinases
- B7-H1 Antigen
- Gene Expression Regulation, Neoplastic
- A549 Cells
- Transforming Growth Factor beta
- Carcinoma, Non-Small-Cell Lung
- Humans
- Female
- Protein Kinase Inhibitors
- Receptors, Transforming Growth Factor beta
- Signal Transduction
詳細情報 詳細情報について
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- CRID
- 1360004239694731776
-
- ISSN
- 17912431
- 1021335X
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- PubMed
- 28849209
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- 資料種別
- journal article
-
- データソース種別
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- Crossref
- KAKEN
- OpenAIRE
