Source data of main figures of the effect of splicing inhibition on antigen presentation
Data files
Jul 15, 2021 version files 12.05 MB
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genediff_B16_IP2.xlsx
2.22 MB
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genediff_B16_ISO.xlsx
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genediff_MCA_IP2.xlsx
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genediff_MCA_ISO.xlsx
3.80 MB
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Source_data_Figure_1.xlsx
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Source_data_Figure_2.xlsx
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Source_data_Figure_3.xlsx
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Source_data_Figure_4.xlsx
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Source_data_Figure_5.xlsx
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Source_data_Figure_6.xlsx
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Source_data_Figure_7.xlsx
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Abstract
The success of cancer immunotherapy relies on the induction of an immunoprotective response targeting tumor antigens (TAs) presented on MHC-I molecules. We demonstrated that the splicing inhibitor isoginkgetin and its water-soluble and non-toxic derivative IP2 act at the production stage of the Pioneer Translation Products (PTPs). We showed that IP2 increases PTP-derived antigen presentation in cancer cells in vitro and impairs tumor growth in vivo. IP2 action is long-lasting and dependent on the CD8+ T cell response against TAs. We observed that the antigen repertoire displayed on MHC-I molecules at the surface of MCA205 fibrosarcoma is modified upon treatment with IP2. In particular, IP2 enhances the presentation of an exon-derived epitope from the tumor suppressor nischarin. The combination of IP2 with a peptide vaccine targeting the nischarin-derived epitope showed a synergistic antitumor effect. These findings identify the spliceosome as a druggable target for the development of epitope-based immunotherapies.