XCR1+ DCs are critical for T cell-mediated immunotherapy of chronic viral infections
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- dc.contributor.author Domenjó Vila, Eva, 1993-
- dc.contributor.author Casella, Valentina, 1991-
- dc.contributor.author Iwabuchi, Ryutaro
- dc.contributor.author Fossum, Even
- dc.contributor.author Pedragosa Marín, Mireia, 1988-
- dc.contributor.author Castellví Fernández, Quim
- dc.contributor.author Cebollada Rica, Paula
- dc.contributor.author Kaisho, Tsuneyasu
- dc.contributor.author Terahara, Kazutaka
- dc.contributor.author Bocharov, Gennady A.
- dc.contributor.author Argilaguet Marqués, Jordi, 1977-
- dc.contributor.author Meyerhans, Andreas
- dc.date.accessioned 2023-03-13T07:13:27Z
- dc.date.available 2023-03-13T07:13:27Z
- dc.date.issued 2023
- dc.description.abstract The contribution of cross-presenting XCR1+ dendritic cells (DCs) and SIRPα+ DCs in maintaining T cell function during exhaustion and immunotherapeutic interventions of chronic infections remains poorly characterized. Using the mouse model of chronic LCMV infection, we found that XCR1+ DCs are more resistant to infection and highly activated compared with SIRPα+ DCs. Exploiting XCR1+ DCs via Flt3L-mediated expansion or XCR1-targeted vaccination notably reinvigorates CD8+ T cells and improves virus control. Upon PD-L1 blockade, XCR1+ DCs are not required for the proliferative burst of progenitor exhausted CD8+ T (TPEX) cells but are indispensable to sustain the functionality of exhausted CD8+ T (TEX) cells. Combining anti-PD-L1 therapy with increased frequency of XCR1+ DCs improves functionality of TPEX and TEX subsets, while increase of SIRPα+ DCs dampened their proliferation. Together, this demonstrates that XCR1+ DCs are crucial for the success of checkpoint inhibitor-based therapies through differential activation of exhausted CD8+ T cell subsets.
- dc.description.sponsorship This work was supported by grants from the Spanish Ministry of Science and Innovation (grant No. PID2019-106323RB-I00 AEI//10.13039/501100011033), the “Unidad de Excelencia María de Maeztu” funded by the MCIN and the AEI (DOI: 10.13039/501100011033; Ref: CEX2018-000792-M), “la Caixa” Foundation (HR17-00199), the Russian Science Foundation (grant No. 18-11-00171), and the Research Council of Norway (grant No. 250884).
- dc.format.mimetype application/pdf
- dc.identifier.citation Domenjo-Vila E, Casella V, Iwabuchi R, Fossum E, Pedragosa M, Castellví Q, Cebollada Rica P, Kaisho T, Terahara K, Bocharov G, Argilaguet J, Meyerhans A. XCR1+ DCs are critical for T cell-mediated immunotherapy of chronic viral infections. Cell Rep. 2023 Feb 14;42(2):112123. DOI: 10.1016/j.celrep.2023.112123
- dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2023.112123
- dc.identifier.issn 2211-1247
- dc.identifier.uri http://hdl.handle.net/10230/56165
- dc.language.iso eng
- dc.publisher Elsevier
- dc.relation.ispartof Cell Rep. 2023 Feb 14;42(2):112123
- dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-106323RB-I00
- dc.rights © 2023 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword CP: Immunology
- dc.subject.keyword Flt3L
- dc.subject.keyword LCMV
- dc.subject.keyword SIRPɑ+ DCs
- dc.subject.keyword T cell exhaustion
- dc.subject.keyword XCR1+ DCs
- dc.subject.keyword Anti-PD-L1
- dc.subject.keyword Chronic infection
- dc.subject.keyword Immunotherapy
- dc.subject.keyword Therapeutic vaccination
- dc.title XCR1+ DCs are critical for T cell-mediated immunotherapy of chronic viral infections
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion