論文 - 詳細
| RRC ID | 78451 |
|---|---|
| 著者 | Hirayama A, Tanaka K, Tsutsumi H, Nakanishi T, Yamashita S, Mizusaki S, Ishii Y, Ota K, Yoneshima Y, Iwama E, Okamoto I. |
| タイトル | Regulation of PD-L1 expression in non-small cell lung cancer by interleukin-1β. |
| ジャーナル | Front Immunol |
| Abstract |
INTRODUCTION:Programmed cell death-ligand 1 (PD-L1) is a biomarker for prediction of the clinical efficacy of immune checkpoint inhibitors in various cancer types. The role of cytokines in regulation of PD-L1 expression in tumor cells has not been fully characterized, however. Here we show that interleukin-1β (IL-1β) plays a key role in regulation of PD-L1 expression in non-small cell lung cancer (NSCLC). METHODS:We performed comprehensive screening of cytokine gene expression in NSCLC tissue using available single-cell RNA-Sequence data. Then we examined the role of IL-1β in vitro to elucidate its induction of PD-L1 on NSCLC cells. RESULTS:The IL-1β gene is highly expressed in the tumor microenvironment, particularly in macrophages. The combination of IL-1β and interferon-γ (IFN-γ) induced a synergistic increase in PD-L1 expression in NSCLC cell lines. IL-1β and IFN-γ also cooperatively activated mitogen-activated protein kinase (MAPK) signaling and promoted the binding of downstream transcription factors to the PD-L1 gene promoter. Furthermore, inhibitors of MAPK signaling blocked upregulation of PD-L1 by IL-1β and IFN-γ. DISCUSSION:Our study reports high levels of IL-1β in the tumor microenvironment may cooperate with IFN-γ to induce maximal PD-L1 expression in tumor cells via activation of MAPK signaling, with the IL-1β-MAPK axis being a promising therapeutic target for attenuation of PD-L1-mediated suppression of antitumor immunity. |
| 巻・号 | 14 |
| ページ | 1192861 |
| 公開日 | 2023-1-1 |
| DOI | 10.3389/fimmu.2023.1192861 |
| PMID | 37441079 |
| PMC | PMC10333574 |
| MeSH | B7-H1 Antigen / metabolism Carcinoma, Non-Small-Cell Lung* / drug therapy Cell Line, Tumor Cytokines / therapeutic use Humans Interferon-gamma / metabolism Interleukin-1beta Lung Neoplasms* / pathology Mitogen-Activated Protein Kinases Tumor Microenvironment |
| リソース情報 | |
| ヒト・動物細胞 | II-18(RCB2093) |