Tumor ablation plus co-administration of CpG and saponin adjuvants affects IL-1 production and multifunctional T cell numbers in tumor draining lymph nodes
| Autor: | Gert Jan Scheffer, Martijn H. den Brok, Tonke K. Raaijmakers, Melissa Wassink, Gosse J. Adema, Stefan Nierkens, Marleen Ansems, Jori A. L. Wagenaars, Renske J.E. van den Bijgaart, Annemarie M.A. de Graaf |
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| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] T cell medicine.medical_treatment T-Lymphocytes Immunology Melanoma Experimental Lymphocyte Activation immunomodulation Mice Antigen Adjuvants Immunologic Interferon medicine Immunology and Allergy Animals RC254-282 Pharmacology Mice Knockout Chemistry Neoplasms. Tumors. Oncology. Including cancer and carcinogens Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] Basic Tumor Immunology Dendritic Cells adaptive immunity Saponins Acquired immune system Combined Modality Therapy Mice Inbred C57BL medicine.anatomical_structure Oncology CpG site Oligodeoxyribonucleotides Cancer research Catheter Ablation Molecular Medicine CD8-positive T-lymphocytes Tumor necrosis factor alpha Female Lymph Nodes Adjuvant CD8 medicine.drug Interleukin-1 |
| Zdroj: | Journal for Immunotherapy of Cancer Journal for Immunotherapy of Cancer, 8 Journal for ImmunoTherapy of Cancer, Vol 8, Iss 1 (2020) Journal for Immunotherapy of Cancer, 8, 1 |
| ISSN: | 2051-1426 |
| Popis: | BackgroundTumor ablation techniques, like cryoablation, are successfully used in the clinic to treat tumors. The tumor debris remaining in situ after ablation is a major antigen depot, including neoantigens, which are presented by dendritic cells (DCs) in the draining lymph nodes to induce tumor-specific CD8+T cells. We have previously shown that co-administration of adjuvants is essential to evoke strong in vivo antitumor immunity and the induction of long-term memory. However, which adjuvants most effectively combine with in situ tumor ablation remains unclear.Methods and resultsHere, we show that simultaneous administration of cytidyl guanosyl (CpG) with saponin-based adjuvants following cryoablation affects multifunctional T-cell numbers and interleukin (IL)-1 induced polymorphonuclear neutrophil recruitment in the tumor draining lymph nodes, relative to either adjuvant alone. The combination of CpG and saponin-based adjuvants induces potent DC maturation (mainly CpG-mediated), antigen cross-presentation (mainly saponin-based adjuvant mediated), while excretion of IL-1β by DCs in vitro depends on the presence of both adjuvants. Most strikingly, CpG/saponin-based adjuvant exposed DCs potentiate antigen-specific T-cell proliferation resulting in multipotent T cells with increased capacity to produce interferon (IFN)γ, IL-2 and tumor necrosis factor-α in vitro. Also in vivo the CpG/saponin-based adjuvant combination plus cryoablation increased the numbers of tumor-specific CD8+T cells showing enhanced IFNγ production as compared with single adjuvant treatments.ConclusionsCollectively, these data indicate that co-injection of CpG with saponin-based adjuvants after cryoablation induces an increased amount of tumor-specific multifunctional T cells. The combination of saponin-based adjuvants with toll-like receptor 9 adjuvant CpG in a cryoablative setting therefore represents a promising in situ vaccination strategy. |
| Databáze: | OpenAIRE |
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