Identification of a class of non-conventional ER-stress-response-derived immunogenic peptides
| Autor: | Maria Rescigno, Marina Aralla, Chiara Pozzi, Michele Mishto, Giuseppe Penna, Luca Tiraboschi, Valentina Ferrari, Michela Lizier, Laura Marconato, Offer Zeira, Juliane Liepe, Alessia Melacarne |
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| Přispěvatelé: | Melacarne A., Ferrari V., Tiraboschi L., Mishto M., Liepe J., Aralla M., Marconato L., Lizier M., Pozzi C., Zeira O., Penna G., Rescigno M. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Proteasome Endopeptidase Complex medicine.medical_treatment Melanoma Experimental Priming (immunology) CD8-Positive T-Lymphocytes Lymphocyte Activation Article General Biochemistry Genetics and Molecular Biology ER-stress response Dogs Antigen Salmonella Cell Line Tumor Neoplasms vaccine medicine Animals Humans cancer Amino Acid Sequence Osteosarcoma Chemistry Endoplasmic reticulum Cell Membrane Cancer Immunotherapy Endoplasmic Reticulum Stress medicine.disease Immune checkpoint Mice Inbred C57BL tumor antigens Cancer cell Unfolded Protein Response Cancer research Melanocytes Female immunotherapy Neoplasm Grading Peptides CD8 tumor antigen |
| Zdroj: | Cell Reports Melacarne, A, Ferrari, V, Tiraboschi, L, Mishto, M, Liepe, J, Aralla, M, Marconato, L, Lizier, M, Pozzi, C, Zeira, O, Penna, G & Rescigno, M 2021, ' Identification of a class of non-conventional ER-stress-response-derived immunogenic peptides ', Cell Reports, vol. 36, no. 1, 109312 . https://doi.org/10.1016/j.celrep.2021.109312 |
| Popis: | Summary 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. Graphical abstract Highlights • Tumor cell infection with Salmonella induces the release of immunogenic peptides • Peptide-based vaccine boosts a strong antitumor response in dog osteosarcoma • MS analysis identified shared peptides released by human melanoma cell lines • Twelve identified peptides are capable of inducing a tumor-specific CD8 response Melacarne et al. demonstrate that Salmonella exacerbates endoplasmic reticulum stress in tumor cells, which induces hemichannel opening and the subsequent release of peptides in the extracellular milieu. Released peptides are immunogenic, shared among tumors, and can be exploited as an anticancer vaccine to prevent metastasis occurrence. |
| Databáze: | OpenAIRE |
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