Tumor ablation plus co-administration of CpG and saponin adjuvants affects IL-1 production and multifunctional T cell numbers in tumor draining lymph nodes
Raaijmakers, Tonke K; van den Bijgaart, Renske J E; den Brok, Martijn H; Wassink, Melissa; de Graaf, Annemarie; Wagenaars, Jori A; Nierkens, Stefan; Ansems, Marleen; Scheffer, Gert Jan; Adema, Gosse J
(2020) Journal for ImmunoTherapy of Cancer, volume 8, issue 1, pp. 1 - 11
(Article)
Abstract
BACKGROUND: Tumor 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
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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 RESULTS: Here, 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. CONCLUSIONS: Collectively, 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.
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Keywords: Adjuvants, Immunologic/administration & dosage, Animals, Catheter Ablation/methods, Combined Modality Therapy, Dendritic Cells/immunology, Female, Interleukin-1/physiology, Lymph Nodes/immunology, Lymphocyte Activation/immunology, Melanoma, Experimental/immunology, Mice, Mice, Inbred C57BL, Mice, Knockout, Oligodeoxyribonucleotides/administration & dosage, Saponins/administration & dosage, T-Lymphocytes/immunology, immunomodulation, CD8-positive T-lymphocytes, adaptive immunity, adjuvants, immunologic, dendritic cells, Molecular Medicine, Oncology, Cancer Research, Immunology and Allergy, Pharmacology, Immunology, Research Support, Non-U.S. Gov't, Journal Article
ISSN: 2051-1426
Publisher: BioMed Central Ltd.
Note: Funding Information: Contributors TR, RvdB, MdB, MW, AdG, JW and SN performed the animal and analytical experiments. MdB, GJS and GA conceived the project. TR, MdB, SN and GA designed the experiments. TR, RvdB, MdB, SN, MA and GA interpreted the data. TR, RvdB, MdB and GA wrote the paper. All authors read and approved the final manuscript. Funding This work was supported by the Dutch Cancer Society (KUN2013-6111) to MdB and GA. Publisher Copyright: © © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
(Peer reviewed)