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PD-L1 Expression and Its Regulation in Lung Adenocarcinoma with ALK Translocation

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Abstract

Background

The mechanism of regulation of PD-L1 expression by ALK translocation remains unclear. We detected PD-L1 protein expression and its regulation in lung adenocarcinoma patients with EML4-ALK fusion gene.

Methods

PD-L1 and ALK expression at protein level in human lung adenocarcinoma cell lines and tumor tissue specimens was evaluated by immunohistochemistry analysis and Western blotting. The expression at DNA level and RNA level was indicated by quantitative real-time PCR analysis. The signal pathway was indicated at protein level by western blotting.

Results

The PD-L1 protein expression was higher in human lung adenocarcinoma cell lines with EML4-ALK fusion gene than that without this fusion gene. Induced expression of EML4-ALK in A549 cells significantly increased PD-L1 protein expression, whereas PD-L1 protein expression was downregulated after crizotinib and pembrolizumab successively. Significant positive correlations between PD-L1 and p-ERK, p-STAT3 or p-AKT expression were observed in ALK-translocated tumors. PD-L1 overexpression was significantly associated with shorter progressive survival and overall survival after crizotinib in ALK-translocated patients.

Conclusions

We demonstrate that ALK translocation can upregulate PD-L1 expression by activating ERK, STAT3 and AKT pathways. ALK inhibitor combined with a PD-L1-targeted therapy may be a potential strategy in ALK-translocated lung adenocarcinoma patients.

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Abbreviations

IHC:

Immunohistochemistry

EGFR:

Epidermal growth factor receptor

EML4-ALK:

Echinoderm microtubule-associated protein like4-an aplastic lymphoma kinase

NSCLC:

Non-small cell lung cancer

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Acknowledgements

We are indebted to Guanting Lv PhD. for his helpful advice regarding to the possible relationship between PD-L1 and ALK. We would like to thank all patients in our study. We are indebted to Dr. Muhammad Jabran for his careful English assistance during the preparation of the manuscript.

Funding

This study is supported by Capital health development scientific research fund-the young talents program (2018-4-1043); Beijing Municipal Administration of Hospitals’ Youth program (QML20181602); Backbone talents project in Beijing Chest Hospital & Beijing Tuberculosis and Thoracic Tumor Research Institute (212-20180307); Municipal Administration of Beijing Chest Hospitals’ Incubating Program (PYZL201706).

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Author notes

  1. Li Ma and Jialin Lv contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, No. 97 Ma Chang, Tongzhou District, Beijing, 101149, China

    Li Ma, Jialin Lv, Xinyong Zhang, Xi Li, Hui Zhang, Jingying Nong, Quan Zhang, Na Qin, Xinjie Yang, Jinghui Wang & Shucai Zhang

  2. Departments of Pathology, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing Chest Hospital, Capital Medical University, Beijing, 101149, China

    Yujie Dong

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  1. Li Ma
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Contributions

Conceived and designed the experiments: LM, JW and SZ. Performed the experiments: LM, HZ, XL, QZ, XY and YD. Analyzed the data: LM and JL. Contributed reagents/materials/analysis tools: XZ, JN, and YD. Wrote the paper: LM and JL.

Corresponding authors

Correspondence to Jinghui Wang or Shucai Zhang.

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No potential conflicts of interest were disclosed.

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Ma, L., Lv, J., Dong, Y. et al. PD-L1 Expression and Its Regulation in Lung Adenocarcinoma with ALK Translocation. Interdiscip Sci Comput Life Sci 11, 266–272 (2019). https://doi.org/10.1007/s12539-019-00331-0

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  • DOI: https://doi.org/10.1007/s12539-019-00331-0

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