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Critical role for Sec22b-dependent antigen cross-presentation in antitumor immunity.

ABSTRACT: CD8+ T cells mediate antigen-specific immune responses that can induce rejection of solid tumors. In this process, dendritic cells (DCs) are thought to take up tumor antigens, which are processed into peptides and loaded onto MHC-I molecules, a process called "cross-presentation." Neither the actual contribution of cross-presentation to antitumor immune responses nor the intracellular pathways involved in vivo are clearly established because of the lack of experimental tools to manipulate this process. To develop such tools, we generated mice bearing a conditional DC-specific mutation in the sec22b gene, a critical regulator of endoplasmic reticulum-phagosome traffic required for cross-presentation. DCs from these mice show impaired cross-presentation ex vivo and defective cross-priming of CD8+ T cell responses in vivo. These mice are also defective for antitumor immune responses and are resistant to treatment with anti-PD-1. We conclude that Sec22b-dependent cross-presentation in DCs is required to initiate CD8+ T cell responses to dead cells and to induce effective antitumor immune responses during anti-PD-1 treatment in mice.

SUBMITTER: Alloatti A

PROVIDER: S-EPMC5551575 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Critical role for Sec22b-dependent antigen cross-presentation in antitumor immunity.

Alloatti Andrés A Rookhuizen Derek C DC Joannas Leonel L Carpier Jean-Marie JM Iborra Salvador S Magalhaes Joao G JG Yatim Nader N Kozik Patrycja P Sancho David D Albert Matthew L ML Amigorena Sebastian S

The Journal of experimental medicine 20170629 8

CD8<sup>+</sup> T cells mediate antigen-specific immune responses that can induce rejection of solid tumors. In this process, dendritic cells (DCs) are thought to take up tumor antigens, which are processed into peptides and loaded onto MHC-I molecules, a process called "cross-presentation." Neither the actual contribution of cross-presentation to antitumor immune responses nor the intracellular pathways involved in vivo are clearly established because of the lack of experimental tools to manipu ...[more]

PMID: 28663435

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Critical role for Sec22b-dependent antigen cross-presentation in antitumor immunity.

Publications

Critical role for Sec22b-dependent antigen cross-presentation in antitumor immunity.

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