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Article

Chemotherapy enhances programmed cell death 1/ligand 1 expression via TGF-β induced epithelial mesenchymal transition in non-small cell lung cancer

  • Authors:
    • Soichiro Funaki
    • Yasushi Shintani
    • Tomohiro Kawamura
    • Ryu Kanzaki
    • Masato Minami
    • Meinoshin Okumura
  • View Affiliations / Copyright

    Affiliations: Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka 565-0897, Japan
  • Pages: 2277-2284
    |
    Published online on: August 9, 2017
       https://doi.org/10.3892/or.2017.5894
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Abstract

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 (P<0.05). 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.
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Copy and paste a formatted citation
Spandidos Publications style
Funaki S, Shintani Y, Kawamura T, Kanzaki R, Minami M and Okumura M: Chemotherapy enhances programmed cell death 1/ligand 1 expression via TGF-β induced epithelial mesenchymal transition in non-small cell lung cancer. Oncol Rep 38: 2277-2284, 2017.
APA
Funaki, S., Shintani, Y., Kawamura, T., Kanzaki, R., Minami, M., & Okumura, M. (2017). Chemotherapy enhances programmed cell death 1/ligand 1 expression via TGF-β induced epithelial mesenchymal transition in non-small cell lung cancer. Oncology Reports, 38, 2277-2284. https://doi.org/10.3892/or.2017.5894
MLA
Funaki, S., Shintani, Y., Kawamura, T., Kanzaki, R., Minami, M., Okumura, M."Chemotherapy enhances programmed cell death 1/ligand 1 expression via TGF-β induced epithelial mesenchymal transition in non-small cell lung cancer". Oncology Reports 38.4 (2017): 2277-2284.
Chicago
Funaki, S., Shintani, Y., Kawamura, T., Kanzaki, R., Minami, M., Okumura, M."Chemotherapy enhances programmed cell death 1/ligand 1 expression via TGF-β induced epithelial mesenchymal transition in non-small cell lung cancer". Oncology Reports 38, no. 4 (2017): 2277-2284. https://doi.org/10.3892/or.2017.5894
Copy and paste a formatted citation
x
Spandidos Publications style
Funaki S, Shintani Y, Kawamura T, Kanzaki R, Minami M and Okumura M: Chemotherapy enhances programmed cell death 1/ligand 1 expression via TGF-β induced epithelial mesenchymal transition in non-small cell lung cancer. Oncol Rep 38: 2277-2284, 2017.
APA
Funaki, S., Shintani, Y., Kawamura, T., Kanzaki, R., Minami, M., & Okumura, M. (2017). Chemotherapy enhances programmed cell death 1/ligand 1 expression via TGF-β induced epithelial mesenchymal transition in non-small cell lung cancer. Oncology Reports, 38, 2277-2284. https://doi.org/10.3892/or.2017.5894
MLA
Funaki, S., Shintani, Y., Kawamura, T., Kanzaki, R., Minami, M., Okumura, M."Chemotherapy enhances programmed cell death 1/ligand 1 expression via TGF-β induced epithelial mesenchymal transition in non-small cell lung cancer". Oncology Reports 38.4 (2017): 2277-2284.
Chicago
Funaki, S., Shintani, Y., Kawamura, T., Kanzaki, R., Minami, M., Okumura, M."Chemotherapy enhances programmed cell death 1/ligand 1 expression via TGF-β induced epithelial mesenchymal transition in non-small cell lung cancer". Oncology Reports 38, no. 4 (2017): 2277-2284. https://doi.org/10.3892/or.2017.5894
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