IGFBP2 regulates PD-L1 expression by activating the EGFR-STAT3 signaling pathway in malignant melanoma
| Autor: | Xu Bai, Xinwei Zhang, Jilong Yang, Gang Zhao, Liang Liu, Chao Zhang, Ting Li, Wei Zhang, Mengze Hao, Da Yang, Min Zhang, Kexin Chen, Farideh Mehraein-Ghomi, Hong Zheng, Shafat Hassan |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
STAT3 Transcription Factor Cancer Research medicine.medical_treatment Regulator Kaplan-Meier Estimate Antibodies Monoclonal Humanized Stat3 Signaling Pathway Article B7-H1 Antigen 03 medical and health sciences 0302 clinical medicine Immune system Downregulation and upregulation PD-L1 Cell Line Tumor medicine Humans Molecular Targeted Therapy Melanoma Cell Nucleus biology business.industry Immunotherapy medicine.disease ErbB Receptors Gene Expression Regulation Neoplastic Insulin-Like Growth Factor Binding Protein 2 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research biology.protein Signal transduction business Signal Transduction |
| Zdroj: | Cancer Lett |
| Popis: | Immunotherapy targeting the PD-1/PD-L1 receptor has achieved great success in melanoma patients. Although many studies have addressed the underlying mechanisms involved in the blockade of PD-1/PD-L1 and the consequent modulation of the immune system, the mechanisms of PD-L1 upregulation and reliable biomarkers to predict the efficacy of anti-PD-1/PD-L1 therapy remain unknown. The present study demonstrates the correlation between IGFBP2 and PD-L1, revealing a novel immune-associated tumor function of IGFBP2 in facilitating nuclear accumulation of EGFR and activation of the EGFR/STAT3/PD-L1 signaling pathway in melanoma cells. Our results also suggest that combined IGFBP2 and PD-L1 expression has the potential to predict the efficacy of anti-PD-1 treatment for malignant melanoma; because the combination of high IGFBP2 and PD-L1 expression characterizes melanoma patients with worse overall survival and is associated with a better immune ecosystem. These characteristics have been confirmed by both in vitro and in vivo data. Consequently, IGFBP2 regulates PD-L1 expression by activating the EGFR-STAT3 signaling pathway and its function as a PD-L1 regulator might suggest novel therapeutic approach for melanoma. |
| Databáze: | OpenAIRE |
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