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The anti-tumor effects of cetuximab in combination with VTX-2337 are T cell dependent
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 (...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810827/ https://www.ncbi.nlm.nih.gov/pubmed/33452311 http://dx.doi.org/10.1038/s41598-020-80957-z |
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author | Cheng, Yinwen Borcherding, Nicholas Ogunsakin, Ayomide Lemke-Miltner, Caitlin D. Gibson-Corley, Katherine N. Rajan, Anand Choi, Allen B. Wongpattaraworakul, Wattawan Chan, Carlos H. F. Salem, Aliasger K. Weiner, George J. Simons, Andrean L. |
author_facet | Cheng, Yinwen Borcherding, Nicholas Ogunsakin, Ayomide Lemke-Miltner, Caitlin D. Gibson-Corley, Katherine N. Rajan, Anand Choi, Allen B. Wongpattaraworakul, Wattawan Chan, Carlos H. F. Salem, Aliasger K. Weiner, George J. Simons, Andrean L. |
author_sort | Cheng, Yinwen |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7810827 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-78108272021-01-21 The anti-tumor effects of cetuximab in combination with VTX-2337 are T cell dependent Cheng, Yinwen Borcherding, Nicholas Ogunsakin, Ayomide Lemke-Miltner, Caitlin D. Gibson-Corley, Katherine N. Rajan, Anand Choi, Allen B. Wongpattaraworakul, Wattawan Chan, Carlos H. F. Salem, Aliasger K. Weiner, George J. Simons, Andrean L. Sci Rep Article 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. Nature Publishing Group UK 2021-01-15 /pmc/articles/PMC7810827/ /pubmed/33452311 http://dx.doi.org/10.1038/s41598-020-80957-z Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Cheng, Yinwen Borcherding, Nicholas Ogunsakin, Ayomide Lemke-Miltner, Caitlin D. Gibson-Corley, Katherine N. Rajan, Anand Choi, Allen B. Wongpattaraworakul, Wattawan Chan, Carlos H. F. Salem, Aliasger K. Weiner, George J. Simons, Andrean L. The anti-tumor effects of cetuximab in combination with VTX-2337 are T cell dependent |
title | The anti-tumor effects of cetuximab in combination with VTX-2337 are T cell dependent |
title_full | The anti-tumor effects of cetuximab in combination with VTX-2337 are T cell dependent |
title_fullStr | The anti-tumor effects of cetuximab in combination with VTX-2337 are T cell dependent |
title_full_unstemmed | The anti-tumor effects of cetuximab in combination with VTX-2337 are T cell dependent |
title_short | The anti-tumor effects of cetuximab in combination with VTX-2337 are T cell dependent |
title_sort | anti-tumor effects of cetuximab in combination with vtx-2337 are t cell dependent |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810827/ https://www.ncbi.nlm.nih.gov/pubmed/33452311 http://dx.doi.org/10.1038/s41598-020-80957-z |
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