Eva Vindevogel1, Thaïs Baert1,2, Anaïs VAN Hoylandt1,2, Godelieve Verbist3, Greetje Vande Velde4, Abhishek D Garg5, Patricia Agostinis5, Ignace Vergote1,2, A N Coosemans6,2. 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.
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. Copyright
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. Copyright
Authors: Matteo Riva; Roxanne Wouters; Akila Weerasekera; Sarah Belderbos; David Nittner; Dietmar R Thal; Thaïs Baert; Roberto Giovannoni; Willy Gsell; Uwe Himmelreich; Marc Van Ranst; An Coosemans Journal: Biol Open Date: 2019-09-12 Impact factor: 2.422