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This record contains raw data and scripts (R software) applied to get Figure 5 and Figure S8 related to article “Identification of a class of non-conventional ER-stress response-derived immunogenic peptides (ERStreP)” Immune checkpoint blockade (ICB) has changed the prognosis of previously untreatable tumors. However, a fraction of patients is refractory to ICB therapy. Ongoing efforts to overcome resistance have focused on vaccination strategies using neoepitopes, although these cannot be applied on a large scale due to the "private" nature of cancer mutations. Here we show that infection of tumor cells with Salmonella induces the opening of membrane hemichannels and the release of proteasome-generated peptides in the extracellular milieu via the exacerbation of endoplasmic reticulum (ER)-stress and the unfolded protein response. Peptides released by cancer cells induced a strong antitumor response in vivo, both in mice bearing B16F10 melanomas and in dogs suffering of osteosarcoma and high-grade sarcoma. Mass spectrometry analysis on the supernatant of human melanoma cells revealed 12 released peptides capable of priming healthy donor CD8+ T cells that recognize and kill human melanoma cells in vitro and when xenotransplanted in vivo, but not healthy melanocytes. Hence, we identified a novel class of tumor antigens that are generated in ER-stressed cells, such as tumor cells, and that do not induce central or peripheral tolerance, nor are presented by healthy cells.
Salmonella, Immunotherapy, Tumor antigens, ER-stress response, Cancer Vaccine
Salmonella, Immunotherapy, Tumor antigens, ER-stress response, Cancer Vaccine
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