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In vivo labeling reveals continuous trafficking of TCF-1+ T cells between tumor and lymphoid tissue.

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cam.issuedOnline2022-04-26
dc.contributor.authorLi, Zhi
dc.contributor.authorTuong, Zewen K
dc.contributor.authorDean, Isaac
dc.contributor.authorWillis, Claire
dc.contributor.authorGaspal, Fabrina
dc.contributor.authorFiancette, Rémi
dc.contributor.authorIdris, Suaad
dc.contributor.authorKennedy, Bethany
dc.contributor.authorFerdinand, John R
dc.contributor.authorPeñalver, Ana
dc.contributor.authorCabantous, Mia
dc.contributor.authorMurtuza Baker, Syed
dc.contributor.authorFry, Jeremy W
dc.contributor.authorCarlesso, Gianluca
dc.contributor.authorHammond, Scott A
dc.contributor.authorDovedi, Simon J
dc.contributor.authorHepworth, Matthew R
dc.contributor.authorClatworthy, Menna R
dc.contributor.authorWithers, David R
dc.contributor.orcidLi, Zhi [0000-0002-0583-1116]
dc.contributor.orcidTuong, Zewen K [0000-0002-6735-6808]
dc.contributor.orcidDean, Isaac [0000-0002-4750-5335]
dc.contributor.orcidWillis, Claire [0000-0001-5504-6741]
dc.contributor.orcidGaspal, Fabrina [0000-0001-8828-4594]
dc.contributor.orcidFiancette, Rémi [0000-0003-1531-9770]
dc.contributor.orcidIdris, Suaad [0000-0002-6070-4670]
dc.contributor.orcidKennedy, Bethany [0000-0001-9529-7545]
dc.contributor.orcidFerdinand, John R [0000-0003-0936-0128]
dc.contributor.orcidPeñalver, Ana [0000-0002-5799-6780]
dc.contributor.orcidCabantous, Mia [0000-0002-3530-494X]
dc.contributor.orcidMurtuza Baker, Syed [0000-0002-6633-333X]
dc.contributor.orcidFry, Jeremy W [0000-0003-3689-6606]
dc.contributor.orcidCarlesso, Gianluca [0000-0002-9592-3267]
dc.contributor.orcidHammond, Scott A [0000-0001-5800-4328]
dc.contributor.orcidDovedi, Simon J [0000-0003-0486-1206]
dc.contributor.orcidHepworth, Matthew R [0000-0002-9613-7858]
dc.contributor.orcidClatworthy, Menna R [0000-0002-3340-9828]
dc.contributor.orcidWithers, David R [0000-0003-3757-7594]
dc.date.accessioned2022-05-28T01:02:57Z
dc.date.available2022-05-28T01:02:57Z
dc.date.issued2022-06-06
dc.date.updated2022-05-28T01:02:57Z
dc.descriptionFunder: Lister Institute of Preventative Medicine
dc.descriptionFunder: NIHR Cambridge Biomedical Research Centre
dc.descriptionFunder: AstraZeneca
dc.description.abstractImproving the efficacy of immune checkpoint therapies will require a better understanding of how immune cells are recruited and sustained in tumors. Here, we used the photoconversion of the tumor immune cell compartment to identify newly entering lymphocytes, determine how they change over time, and investigate their egress from the tumor. Combining single-cell transcriptomics and flow cytometry, we found that while a diverse mix of CD8 T cell subsets enter the tumor, all CD8 T cells retained within this environment for more than 72 h developed an exhausted phenotype, revealing the rapid establishment of this program. Rather than forming tumor-resident populations, non-effector subsets, which express TCF-1 and include memory and stem-like cells, were continuously recruited into the tumor, but this recruitment was balanced by concurrent egress to the tumor-draining lymph node. Thus, the TCF-1+ CD8 T cell niche in tumors is highly dynamic, with the circulation of cells between the tumor and peripheral lymphoid tissue to bridge systemic and intratumoral responses.
dc.identifier.doi10.17863/CAM.84994
dc.identifier.eissn1540-9538
dc.identifier.issn0022-1007
dc.identifier.other35472220
dc.identifier.otherPMC9048291
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/337585
dc.languageeng
dc.language.isoeng
dc.publisherRockefeller University Press
dc.publisher.urlhttp://dx.doi.org/10.1084/jem.20210749
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcenlmid: 2985109R
dc.sourceessn: 1540-9538
dc.subjectCD8-Positive T-Lymphocytes
dc.subjectHumans
dc.subjectImmunotherapy
dc.subjectLymphoid Tissue
dc.subjectNeoplasms
dc.subjectT-Lymphocyte Subsets
dc.titleIn vivo labeling reveals continuous trafficking of TCF-1+ T cells between tumor and lymphoid tissue.
dc.typeArticle
dcterms.dateAccepted2022-04-06
prism.issueIdentifier6
prism.publicationNameJ Exp Med
prism.volume219
pubs.funder-project-idMedical Research Council (MR/S035842/1)
pubs.funder-project-idWellcome Trust (220268/Z/20/Z)
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1084/jem.20210749

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