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Unveiling the regulatory mechanism of nimotuzumab on PD-L1 expression in head and neck squamous cell carcinoma patients: Implications for enhanced anticancer treatment strategies.
Hu, Minwan; Tang, Borui; Dai, Yuyang; Zhao, Xiuli.
Afiliación
  • Hu M; School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, PR China; Department of National Institute for Drug Clinical Trial, Affiliated Beijing Tongren Hospital of Capital Medical University, Beijing 100005, PR China.
  • Tang B; School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, PR China; Department of National Institute for Drug Clinical Trial, Affiliated Beijing Tongren Hospital of Capital Medical University, Beijing 100005, PR China.
  • Dai Y; Department of National Institute for Drug Clinical Trial, Affiliated Beijing Tongren Hospital of Capital Medical University, Beijing 100005, PR China.
  • Zhao X; School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, PR China; Department of National Institute for Drug Clinical Trial, Affiliated Beijing Tongren Hospital of Capital Medical University, Beijing 100005, PR China. Electronic address: lilyzhao1028@outlook.com.
Cell Signal ; 121: 111290, 2024 Sep.
Article en En | MEDLINE | ID: mdl-38977231
ABSTRACT
The overexpression of programmed death ligand 1 (PD-L1) is associated with resistance to anticancer therapies and poor prognosis in patients with head and neck squamous cell carcinoma (HNSCC). Nimotuzumab, a humanized anti-epidermal growth factor receptor (EGFR) mAb, has been widely used clinically for treating several solid tumors. However, whether its anticancer effect involves a reduction in PD-L1 expression remains unclear. The current study aimed to investigate the regulatory effects and underlying mechanism of nimotuzumab on PD-L1 expression in HNSCC both in vitro and in vivo. In vitro, nimotuzumab inhibited IFN-γ-induced PD-L1 upregulation at both the transcriptional and protein levels in the HNSCC cell lines. Subsequent mechanism research revealed that nimotuzumab suppressed IFN-γ-stimulated PD-L1 upregulation mainly by inhibiting phosphorylation of EGFR/MEK/ERK pathway, which was further validated by MEK and ERK inhibitors. In a HNSCC tumor-bearing model, nimotuzumab significantly decreased PD-L1 expression during tumor progression or chemotherapy, and this reduction was accompanied by increased sensitivity of the tumor to docetaxel and atezolizumab. Additionally, nimotuzumab reversed PD-L1 upregulation when combined with Taxol + Cisplatin (TP) induction chemotherapy regimens and improved the CD4+ and CD8+ T cells infiltration in HNSCC patients. These findings provide new insights into the anticancer mechanisms of nimotuzumab in HNSCC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anticuerpos Monoclonales Humanizados / Antígeno B7-H1 / Carcinoma de Células Escamosas de Cabeza y Cuello / Neoplasias de Cabeza y Cuello Límite: Animals / Female / Humans / Male Idioma: En Revista: Cell Signal Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anticuerpos Monoclonales Humanizados / Antígeno B7-H1 / Carcinoma de Células Escamosas de Cabeza y Cuello / Neoplasias de Cabeza y Cuello Límite: Animals / Female / Humans / Male Idioma: En Revista: Cell Signal Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido