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  • 标题:The anti-tumor effects of cetuximab in combination with VTX-2337 are T cell dependent
  • 本地全文:下载
  • 作者:Yinwen Cheng ; Nicholas Borcherding ; Ayomide Ogunsakin
  • 期刊名称:Scientific Reports
  • 电子版ISSN:2045-2322
  • 出版年度:2021
  • 卷号:11
  • 期号:1
  • 页码:1535
  • DOI:10.1038/s41598-020-80957-z
  • 出版社:Springer Nature
  • 摘要:Abstract The Toll-like receptor 8 (TLR8) agonist VTX-2337 (motolimod) is an anti-cancer immunotherapeutic agent that is believed to augment natural killer (NK) and dendritic cell (DC) activity. The goal of this work is to examine the role of TLR8 expression/activity in head and neck squamous cell carcinoma (HNSCC) to facilitate the prediction of responders to VTX-2337-based therapy. The prognostic role of TLR8 expression in HNSCC patients was assessed by TCGA and tissue microarray analyses. The anti-tumor effect of VTX-2337 was determined in SCCVII/C3H, mEERL/C57Bl/6 and TUBO-human EGFR/BALB/c syngeneic mouse models. The effect of combined VTX-2337 and cetuximab treatment on tumor growth, survival and immune cell recruitment was assessed. TLR8 expression was associated with CD8 T cell infiltration and favorable survival outcomes. VTX-2337 delayed tumor growth in all 3 syngeneic mouse models and significantly increased the survival of cetuximab-treated mice. The anti-tumor effects of VTX-2337 cetuximab were accompanied by increased splenic lymphoid DCs and IFNγ CD4 and tumor-specific CD8 T cells. Depletion of CD4 T cells, CD8 T cells and NK cells were all able to abolish the anti-tumor effect of VTX-2337 cetuximab. Altogether, VTX-2337 remains promising as an adjuvant for cetuximab-based therapy however patients with high TLR8 expression may be more likely to derive benefit from this drug combination compared to patients with low TLR8 expression.
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