The Use of Toll-like Receptor 4 Agonist to Reshape the Immune Signature in Ovarian Cancer

Eva Vindevogel; Thaïs Baert; Anaïs VAN Hoylandt; Godelieve Verbist; Greetje Vande Velde; Abhishek D Garg; Patricia Agostinis; Ignace Vergote; A N Coosemans

doi:10.21873/anticanres.11162

The Use of Toll-like Receptor 4 Agonist to Reshape the Immune Signature in Ovarian Cancer

Anticancer Res. 2016 Nov;36(11):5781-5792. doi: 10.21873/anticanres.11162.

Authors

Eva Vindevogel¹, Thaïs Baert^{1

2}, Anaïs VAN Hoylandt^{1

2}, Godelieve Verbist³, Greetje Vande Velde⁴, Abhishek D Garg⁵, Patricia Agostinis⁵, Ignace Vergote^{1

2}, A N Coosemans^{6

2}

Affiliations

¹ Laboratory of Tumor Immunology and Immunotherapy, Department of Oncology, ImmunOvar Research Group, KU Leuven, Leuven, Belgium.
² Department of Gynaecology and Obstetrics, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
³ Department of Development and Regeneration, Organ Systems, KU Leuven, Leuven, Belgium.
⁴ Department of Imaging and Pathology, Biomedical MRI/MoSAIC, KU Leuven, Leuven, Belgium.
⁵ Laboratory for Cell Death Research and Therapy (CDRT), Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
⁶ Laboratory of Tumor Immunology and Immunotherapy, Department of Oncology, ImmunOvar Research Group, KU Leuven, Leuven, Belgium an.coosemans@gmail.com.

PMID: 27793900
DOI: 10.21873/anticanres.11162

Abstract

Background: Dendritic cell (DC) mono-immunotherapy has not been successful so far in ovarian cancer. The addition of a toll-like receptor (TLR) agonist has the potential to boost the innate immune system, in addition to the adoptive immune response initiated by DCs.

Materials and methods: ID8-fLuc C57BL/6 mice were injected with DCs loaded with hypericin-based photodynamic therapy-treated tumor lysate. A TLR4 agonist [lipopolysaccharide (LPS)] was administered by different schedules). After two and three DC vaccinations, immune analysis was performed.

Results: There was no survival benefit from therapy with TLR4 agonist. Moreover, if LPS administrations started one week after tumor inoculation, the overall survival was even worse than that of untreated controls. Immune analyses revealed an intratumoral increase in natural killer cells and a decrease in regulatory T-cells, but an immunosuppressive signature in the ascites.

Conclusion: Addition of LPS as an adjuvant to DC immunotherapy of ovarian cancer does not result in survival benefit.

Keywords: DC; Dendritic cell; LPS; TLR4; immunotherapy; mouse; ovarian cancer; toll-like receptor.

MeSH terms

Animals
Female
Immunotherapy
Mice
Mice, Inbred C57BL
Ovarian Neoplasms / immunology
Ovarian Neoplasms / therapy*
Toll-Like Receptor 4 / agonists*

Substances

Tlr4 protein, mouse
Toll-Like Receptor 4