Journal article
The anti-tumor effects of cetuximab in combination with VTX-2337 are T cell dependent
Scientific reports, Vol.11(1), pp.1535-1535
12/01/2021
DOI: 10.1038/s41598-020-80957-z
PMCID: PMC7810827
PMID: 33452311
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.
Details
- Title: Subtitle
- The anti-tumor effects of cetuximab in combination with VTX-2337 are T cell dependent
- Creators
- Yinwen Cheng - University of IowaNicholas Borcherding - University of IowaAyomide Ogunsakin - Lincoln University (Pennsylvania)Caitlin D Lemke-Miltner - Iowa City, IA USAKatherine N Gibson-Corley - Iowa City, IA USAAnand Rajan - University of IowaAllen B Choi - University of IowaWattawan Wongpattaraworakul - University of IowaCarlos H. F Chan - University of IowaAliasger K Salem - University of IowaGeorge J Weiner - University of IowaAndrean L Simons - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.11(1), pp.1535-1535
- DOI
- 10.1038/s41598-020-80957-z
- PMID
- 33452311
- PMCID
- PMC7810827
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Publisher
- Nature Publishing Group UK
- Grant note
- NIHR01DE024550 / ;
- Language
- English
- Date published
- 12/01/2021
- Academic Unit
- Dermatology; Oral Pathology, Radiology and Medicine; The University of Iowa Institute for Vision Research; Pathology; Pharmaceutical Sciences and Experimental Therapeutics; Surgery; Craniofacial Anomalies Research Center; Chemical and Biochemical Engineering; Roy J. Carver Department of Biomedical Engineering; Hematology, Oncology, and Blood & Marrow Transplantation; Radiation Oncology; Dental Research; Holden Comprehensive Cancer Center; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9984186422302771
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