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Figure S1-S13 from Sialic Acid Blockade Suppresses Tumor Growth by Enhancing T-cell–Mediated Tumor Immunity

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posted on 2023-03-31, 02:02 authored by Christian Büll, Thomas J. Boltje, Natasja Balneger, Sarah M. Weischer, Melissa Wassink, Jasper J. van Gemst, Victor R. Bloemendal, Louis Boon, Johan van der Vlag, Torben Heise, Martijn H. den Brok, Gosse J. Adema

Fig. S1 Effect of intratumoral injections with 20 mg/kg S1 Ac53FaxNeu5Ac on B16-F10WT tumor growth. Fig. S2 Responsiveness of melanoma and neuroblastoma cells to Ac53FaxNeu5Ac. S2 Fig. S3 10 mg/kg Ac53FaxNeu5Ac injections are well tolerated. S3 Fig. S4 Immune cell infiltration of tumors injected S4 with Ac53FaxNeu5Ac. Fig. S5 Effect of intratumoral Ac53FaxNeu5Ac injections on S5 systemic sialylation. Fig. S6 Effect of intratumoral Ac53FaxNeu5Ac injections on tumor-infiltrating S6 immune cells and immune cell populations in (tumor-draining) lymph nodes and spleen. Fig. S7 Effect of intratumoral Ac53FaxNeu5Ac injections on S7 immune cell populations in (tumor-draining) lymph nodes and spleen. Fig. S8 Depletion of NK cells and CD8+ T cells prior to of B16-F10WT S8 tumor inoculation. Fig. S9 Combination of sialic acid blockade with clodronate liposomes S9 and anti-Gr-1 antibodies. Fig. S10 In vitro killing of Ac53FaxNeu5Ac-treated tumor cells and expression of S10 Siglecs on OT-I T cells Fig. S11 B16-F10OVA cell surface molecule expression and purification S11 and sialylation of OT-I CD8+ T cells. Fig. S12 Systemic effect of sialic acid blockade on CpG-induced S12 dendritic cell maturation. Fig. S13 Systemic effect of sialic acid blockade on CD8+ T cell numbers. S13

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Radboudumc grant

Netherlands Organization for Scientific Research

Marie Skøodowska-Curie Innovative Training Network

KWF

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ARTICLE ABSTRACT

Sialic acid sugars on the surface of cancer cells have emerged as potent immune modulators that contribute to the immunosuppressive microenvironment and tumor immune evasion. However, the mechanisms by which these sugars modulate antitumor immunity as well as therapeutic strategies directed against them are limited. Here we report that intratumoral injections with a sialic acid mimetic Ac53FaxNeu5Ac block tumor sialic acid expression in vivo and suppress tumor growth in multiple tumor models. Sialic acid blockade had a major impact on the immune cell composition of the tumor, enhancing tumor-infiltrating natural killer cell and CD8+ T-cell numbers while reducing regulatory T-cell and myeloid regulatory cell numbers. Sialic acid blockade enhanced cytotoxic CD8+ T-cell–mediated killing of tumor cells in part by facilitating antigen-specific T-cell–tumor cell clustering. Sialic acid blockade also synergized with adoptive transfer of tumor-specific CD8+ T cells in vivo and enhanced CpG immune adjuvant therapy by increasing dendritic cell activation and subsequent CD8+ T-cell responses. Collectively, these data emphasize the crucial role of sialic acids in tumor immune evasion and provide proof of concept that sialic acid blockade creates an immune-permissive tumor microenvironment for CD8+ T-cell–mediated tumor immunity, either as single treatment or in combination with other immune-based intervention strategies.Significance: Sialic acid sugars function as important modulators of the immunosuppressive tumor microenvironment that limit potent antitumor immunity.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/13/3574/F1.large.jpg. Cancer Res; 78(13); 3574–88. ©2018 AACR.

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