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

Autor:	Melacarne A; IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano, Milan, Italy., Ferrari V; Humanitas University, Department of Biomedical Sciences, Via Rita Levi Montalcini, 20072 Pieve Emanuele, Milan, Italy., Tiraboschi L; IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano, Milan, Italy., Mishto M; King's College London, Centre for Inflammation Biology and Cancer Immunology, Peter Gorer Department of Immunobiology, Great Maze Pond, SE1 1UL London, UK; Francis Crick Institute, NW1 1AT London, UK., Liepe J; Max-Planck-Institute for Biophysical Chemistry, Am Faßberg 11, 37077 Göttingen, Germany., Aralla M; Pronto Soccorso Veterinario Laudense, Via Milano 22, 26900 Lodi, Italy., Marconato L; University of Bologna, Department of Veterinary Medical Science, via Tolara di Sopra, 40064 Ozzano dell'Emilia, Bologna, Italy., Lizier M; IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano, Milan, Italy., Pozzi C; IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano, Milan, Italy., Zeira O; San Michele Veterinary Hospital, via I maggio 26838 Tavazzano con Villavesco, Lodi, Italy., Penna G; IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano, Milan, Italy., Rescigno M; IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano, Milan, Italy; Humanitas University, Department of Biomedical Sciences, Via Rita Levi Montalcini, 20072 Pieve Emanuele, Milan, Italy. Electronic address: maria.rescigno@hunimed.eu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2021 Jul 06; Vol. 36 (1), pp. 109312.
DOI:	10.1016/j.celrep.2021.109312
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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