Identification of a class of non-conventional ER-stress-response-derived immunogenic peptides

Efforts to overcome resistance to immune checkpoint blockade therapy have focused on vaccination strategies using neoepitopes, although they 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 extracellular release of proteasome-generated peptides by the exacerbation of endoplasmic reticulum (ER) stress. Peptides released by cancer cells foster an antitumor response in vivo, both in mice bearing B16F10 melanomas and in dogs suffering from osteosarcoma. Mass spectrometry analysis on the supernatant of human melanoma cells revealed 12 peptides capable of priming healthy-donor CD8(+) T cells that recognize and kill human melanoma cells in vitro and when xenotransplanted in vivo. Hence, we identified a class of shared tumor antigens that are generated in ER-stressed cells, such as tumor cells, that do not induce tolerance and are not presented by healthy cells.

Automated summary

Infection of tumor cells with Salmonella induces the release of peptides that promote an antitumor response, applicable to both melanoma and osteosarcoma. Mass spectrometry analysis revealed a class of shared tumor antigens generated in ER-stressed cells, which do not induce tolerance and are effective in promoting the immune response against cancer cells.