{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:03:52Z","timestamp":1787007832839,"version":"build-2736575974"},"reference-count":48,"publisher":"Rockefeller University Press","issue":"9","license":[{"start":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T00:00:00Z","timestamp":1592179200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.rupress.org\/terms\/"},{"start":{"date-parts":[[2021,3,7]],"date-time":"2021-03-07T00:00:00Z","timestamp":1615075200000},"content-version":"vor","delay-in-days":265,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007878","name":"Diabetes Research Center","doi-asserted-by":"publisher","award":["P30 DK063720"],"award-info":[{"award-number":["P30 DK063720"]}],"id":[{"id":"10.13039\/100007878","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R21AR72195"],"award-info":[{"award-number":["R21AR72195"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Human Frontiers Science Program","award":["LT000183\/2018-L"],"award-info":[{"award-number":["LT000183\/2018-L"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5T32DK007573"],"award-info":[{"award-number":["5T32DK007573"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,9,7]]},"abstract":"<jats:p>Tumor-infiltrating CD8+ T cells mediate antitumor immune responses. However, the mechanisms by which T cells remain poised to kill cancer cells despite expressing high levels of inhibitory receptors are unknown. Here, we report that layilin, a C-type lectin domain\u2013containing membrane glycoprotein, is selectively expressed on highly activated, clonally expanded, but phenotypically exhausted CD8+\u00a0T cells in human melanoma. Lineage-specific deletion of layilin on murine CD8+ T cells reduced their accumulation in tumors and increased tumor growth in vivo. Congruently, gene editing of LAYN in human CD8+ T cells reduced direct tumor cell killing ex vivo. On a molecular level, layilin colocalized with integrin \u03b1L\u03b22 (LFA-1) on T cells, and cross-linking layilin promoted the activated state of this integrin. Accordingly, LAYN deletion resulted in attenuated LFA-1\u2013dependent cellular adhesion. Collectively, our results identify layilin as part of a molecular pathway in which exhausted or \u201cdysfunctional\u201d CD8+\u00a0T cells enhance cellular adhesiveness to maintain their cytotoxic potential.<\/jats:p>","DOI":"10.1084\/jem.20192080","type":"journal-article","created":{"date-parts":[[2020,4,11]],"date-time":"2020-04-11T02:21:18Z","timestamp":1586571678000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":64,"title":["Layilin augments integrin activation to promote antitumor immunity"],"prefix":"10.1084","volume":"217","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2544-5191","authenticated-orcid":true,"given":"Kelly M.","family":"Mahuron","sequence":"first","affiliation":[{"name":"Department of Surgery, University of California, San Francisco, San Francisco, CA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1227-1508","authenticated-orcid":false,"given":"Joshua M.","family":"Moreau","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California, San Francisco, San Francisco, CA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff E.","family":"Glasgow","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devi P.","family":"Boda","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California, San Francisco, San Francisco, CA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariela L.","family":"Pauli","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California, San Francisco, San Francisco, CA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoire","family":"Gouirand","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California, San Francisco, San Francisco, CA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luv","family":"Panjabi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California, San Francisco, San Francisco, CA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robby","family":"Grewal","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California, San Francisco, San Francisco, CA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob M.","family":"Luber","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, Harvard Medical School, Boston, MA 4"},{"name":"Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anubhav N.","family":"Mathur","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California, San Francisco, San Francisco, CA 2"},{"name":"T-REX Bio, Burlingame, CA 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renny M.","family":"Feldman","sequence":"additional","affiliation":[{"name":"T-REX Bio, Burlingame, CA 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Shifrut","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8466-7424","authenticated-orcid":true,"given":"Pooja","family":"Mehta","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California, San Francisco, San Francisco, CA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret M.","family":"Lowe","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California, San Francisco, San Francisco, CA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Alvarado","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California, San Francisco, San Francisco, CA 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Marson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 7"},{"name":"Chan Zuckerberg Biohub, San Francisco, CA 8"},{"name":"Parker Institute for Cancer Immunotherapy, San Francisco, CA 9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meromit","family":"Singer","sequence":"additional","affiliation":[{"name":"Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA 5"},{"name":"Department of Immunology, Harvard Medical School, Boston, MA 10"},{"name":"Dana-Farber Cancer Institute, Boston, MA 11"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim","family":"Wells","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ray","family":"Jupp","sequence":"additional","affiliation":[{"name":"T-REX Bio, Burlingame, CA 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6617-8421","authenticated-orcid":true,"given":"Adil I.","family":"Daud","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Francisco, San Francisco, CA 12"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0462-5732","authenticated-orcid":true,"given":"Michael D.","family":"Rosenblum","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of California, San Francisco, San Francisco, CA 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2020,6,15]]},"reference":[{"key":"2023072617484058300_bib1","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1146\/annurev.immunol.021908.132554","article-title":"The ins and outs of leukocyte integrin signaling","volume":"27","author":"Abram","year":"2009","journal-title":"Annu. Rev. Immunol"},{"key":"2023072617484058300_bib2","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1038\/s41586-019-1326-9","article-title":"TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection","volume":"571","author":"Alfei","year":"2019","journal-title":"Nature"},{"key":"2023072617484058300_bib3","doi-asserted-by":"publisher","first-page":"6437","DOI":"10.1073\/pnas.0502467102","article-title":"Distinct role of lymphocyte function-associated antigen-1 in mediating effective cytolytic activity by cytotoxic T lymphocytes","volume":"102","author":"Anikeeva","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023072617484058300_bib4","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1091\/mbc.12.4.891","article-title":"Layilin, a novel integral membrane protein, is a hyaluronan receptor","volume":"12","author":"Bono","year":"2001","journal-title":"Mol. Biol. Cell"},{"key":"2023072617484058300_bib5","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1083\/jcb.143.2.429","article-title":"Layilin, a novel talin-binding transmembrane protein homologous with C-type lectins, is localized in membrane ruffles","volume":"143","author":"Borowsky","year":"1998","journal-title":"J. Cell Biol"},{"key":"2023072617484058300_bib6","doi-asserted-by":"publisher","first-page":"6898","DOI":"10.1038\/ncomms7898","article-title":"Regulation of endogenous transmembrane receptors through optogenetic Cry2 clustering","volume":"6","author":"Bugaj","year":"2015","journal-title":"Nat. Commun"},{"key":"2023072617484058300_bib7","doi-asserted-by":"publisher","first-page":"14727","DOI":"10.1073\/pnas.1008663107","article-title":"Requirement of open headpiece conformation for activation of leukocyte integrin alphaXbeta2","volume":"107","author":"Chen","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023072617484058300_bib8","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1126\/science.1231143","article-title":"Multiplex genome engineering using CRISPR\/Cas systems","volume":"339","author":"Cong","year":"2013","journal-title":"Science"},{"key":"2023072617484058300_bib9","doi-asserted-by":"publisher","first-page":"3447","DOI":"10.1172\/JCI87324","article-title":"Tumor immune profiling predicts response to anti-PD-1 therapy in human melanoma","volume":"126","author":"Daud","year":"2016","journal-title":"J. Clin. Invest"},{"key":"2023072617484058300_bib10","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1016\/j.immuni.2016.10.021","article-title":"Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells","volume":"45","author":"De Simone","year":"2016","journal-title":"Immunity"},{"key":"2023072617484058300_bib11","first-page":"2322","article-title":"Tumor angiogenesis modulates leukocyte-vessel wall interactions in vivo by reducing endothelial adhesion molecule expression","volume":"63","author":"Dirkx","year":"2003","journal-title":"Cancer Res"},{"key":"2023072617484058300_bib12","doi-asserted-by":"publisher","first-page":"2724","DOI":"10.1038\/s41467-018-05072-0","article-title":"Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors","volume":"9","author":"Duhen","year":"2018","journal-title":"Nat. Commun"},{"key":"2023072617484058300_bib13","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/laban.254","article-title":"Estimation of rat mammary tumor volume using caliper and ultrasonography measurements","volume":"42","author":"Faustino-Rocha","year":"2013","journal-title":"Lab Anim. (NY)"},{"key":"2023072617484058300_bib14","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1158\/0008-5472.CAN-12-2569","article-title":"CD103 or LFA-1 engagement at the immune synapse between cytotoxic T cells and tumor cells promotes maturation and regulates T-cell effector functions","volume":"73","author":"Franciszkiewicz","year":"2013","journal-title":"Cancer Res"},{"key":"2023072617484058300_bib15","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1038\/s41591-018-0045-3","article-title":"Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing","volume":"24","author":"Guo","year":"2018","journal-title":"Nat. Med"},{"key":"2023072617484058300_bib16","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1146\/annurev-immunol-042718-041341","article-title":"Origin, Organization, Dynamics, and Function of Actin and Actomyosin Networks at the T Cell Immunological Synapse","volume":"37","author":"Hammer","year":"2019","journal-title":"Annu. Rev. Immunol"},{"key":"2023072617484058300_bib17","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.3389\/fimmu.2019.01078","article-title":"Cell adhesion molecules and their roles and regulation in the immune and tumor microenvironment","volume":"10","author":"Harjunp\u00e4\u00e4","year":"2019","journal-title":"Front. Immunol"},{"key":"2023072617484058300_bib18","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1038\/s41591-019-0357-y","article-title":"A single dose of neoadjuvant PD-1 blockade predicts clinical outcomes in resectable melanoma","volume":"25","author":"Huang","year":"2019","journal-title":"Nat. Med"},{"key":"2023072617484058300_bib19","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/nature19330","article-title":"Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy","volume":"537","author":"Im","year":"2016","journal-title":"Nature"},{"key":"2023072617484058300_bib20","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1126\/science.283.5401.543","article-title":"Prevention of constitutive TNF receptor 1 signaling by silencer of death domains","volume":"283","author":"Jiang","year":"1999","journal-title":"Science"},{"key":"2023072617484058300_bib21","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.36967","article-title":"Topography of cancer-associated immune cells in human solid tumors","volume":"7","author":"Kather","year":"2018","journal-title":"eLife"},{"key":"2023072617484058300_bib22","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/s41586-019-1325-x","article-title":"TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion","volume":"571","author":"Khan","year":"2019","journal-title":"Nature"},{"key":"2023072617484058300_bib49","unstructured":"Kolde, R.\n          \n          2015. Pheatmap: pretty heatmaps. R Package Version 1.0.12. https:\/\/rdrr.io\/cran\/pheatmap\/"},{"key":"2023072617484058300_bib23","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.93433","article-title":"Partially exhausted tumor-infiltrating lymphocytes predict response to combination immunotherapy","volume":"2","author":"Loo","year":"2017","journal-title":"JCI Insight"},{"key":"2023072617484058300_bib24","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1038\/nature25501","article-title":"TGF\u03b2 attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells","volume":"554","author":"Mariathasan","year":"2018","journal-title":"Nature"},{"key":"2023072617484058300_bib25","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1158\/2159-8290.CD-13-0985","article-title":"T-cell and NK-cell infiltration into solid tumors: a key limiting factor for efficacious cancer immunotherapy","volume":"4","author":"Melero","year":"2014","journal-title":"Cancer Discov"},{"key":"2023072617484058300_bib26","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1038\/s41586-018-0812-9","article-title":"Tissue-resident memory CD8+ T cells promote melanoma-immune equilibrium in skin","volume":"565","author":"Park","year":"2019","journal-title":"Nature"},{"key":"2023072617484058300_bib27","doi-asserted-by":"publisher","first-page":"E4041","DOI":"10.1073\/pnas.1720948115","article-title":"Macrophages impede CD8 T cells from reaching tumor cells and limit the efficacy of anti-PD-1 treatment","volume":"115","author":"Peranzoni","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023072617484058300_bib28","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/s41586-018-0326-5","article-title":"Reprogramming human T cell function and specificity with non-viral genome targeting","volume":"559","author":"Roth","year":"2018","journal-title":"Nature"},{"key":"2023072617484058300_bib29","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1038\/s41591-018-0078-7","article-title":"Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis","volume":"24","author":"Savas","year":"2018","journal-title":"Nat. Med"},{"key":"2023072617484058300_bib30","doi-asserted-by":"publisher","first-page":"10437","DOI":"10.1073\/pnas.1512503112","article-title":"Generation of knock-in primary human T cells using Cas9 ribonucleoproteins","volume":"112","author":"Schumann","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023072617484058300_bib31","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41586-019-1324-y","article-title":"TOX is a critical regulator of tumour-specific T cell differentiation","volume":"571","author":"Scott","year":"2019","journal-title":"Nature"},{"key":"2023072617484058300_bib32","doi-asserted-by":"publisher","first-page":"1958","DOI":"10.1016\/j.cell.2018.10.024","article-title":"Genome-wide CRISPR Screens in Primary Human T Cells Reveal Key Regulators of Immune Function","volume":"175","author":"Shifrut","year":"2018","journal-title":"Cell"},{"key":"2023072617484058300_bib33","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1038\/s41586-018-0130-2","article-title":"Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates","volume":"557","author":"Simoni","year":"2018","journal-title":"Nature"},{"key":"2023072617484058300_bib34","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1038\/nmeth947","article-title":"Direct observation of individual endogenous protein complexes in situ by proximity ligation","volume":"3","author":"S\u00f6derberg","year":"2006","journal-title":"Nat. Methods"},{"key":"2023072617484058300_bib35","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive Integration of Single-Cell Data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"2023072617484058300_bib36","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023072617484058300_bib37","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/s41556-018-0234-9","article-title":"Integrin activation by talin, kindlin and mechanical forces","volume":"21","author":"Sun","year":"2019","journal-title":"Nat. Cell Biol"},{"key":"2023072617484058300_bib38","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1038\/s41591-018-0057-z","article-title":"A transcriptionally and functionally distinct PD-1+ CD8+ T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade","volume":"24","author":"Thommen","year":"2018","journal-title":"Nat. Med"},{"key":"2023072617484058300_bib39","doi-asserted-by":"publisher","first-page":"952","DOI":"10.3389\/fimmu.2018.00952","article-title":"LFA-1 in T cell migration and differentiation","volume":"9","author":"Walling","year":"2018","journal-title":"Front. Immunol"},{"key":"2023072617484058300_bib40","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.jmb.2008.06.087","article-title":"Structural basis for the interaction between the cytoplasmic domain of the hyaluronate receptor layilin and the talin F3 subdomain","volume":"382","author":"Wegener","year":"2008","journal-title":"J. Mol. Biol"},{"key":"2023072617484058300_bib41","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1158\/2159-8290.CD-18-0367","article-title":"Fundamental mechanisms of immune checkpoint blockade therapy","volume":"8","author":"Wei","year":"2018","journal-title":"Cancer Discov"},{"key":"2023072617484058300_bib42","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1016\/j.immuni.2007.09.006","article-title":"Molecular signature of CD8+ T cell exhaustion during chronic viral infection","volume":"27","author":"Wherry","year":"2007","journal-title":"Immunity"},{"key":"2023072617484058300_bib50","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-24277-4","volume-title":"ggplot2: Elegant Graphics for Data Analysis","author":"Wickham","year":"2016"},{"key":"2023072617484058300_bib43","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1038\/s41591-019-0522-3","article-title":"Clonal replacement of tumor-specific T cells following PD-1 blockade","volume":"25","author":"Yost","year":"2019","journal-title":"Nat. Med"},{"key":"2023072617484058300_bib44","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1111\/j.1365-2567.2011.03549.x","article-title":"Integrin signalling and function in immune cells","volume":"135","author":"Zhang","year":"2012","journal-title":"Immunology"},{"key":"2023072617484058300_bib45","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1016\/j.cell.2017.05.035","article-title":"Landscape of Infiltrating T Cells in Liver Cancer Revealed by Single-Cell Sequencing","volume":"169","author":"Zheng","year":"2017","journal-title":"Cell"},{"key":"2023072617484058300_bib46","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1038\/ng750","article-title":"Epigenetic silencing of CD4 in T cells committed to the cytotoxic lineage","volume":"29","author":"Zou","year":"2001","journal-title":"Nat. Genet"}],"container-title":["Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20192080\/1780578\/jem_20192080.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/doi\/10.1084\/jem.20192080\/1780578\/jem_20192080.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T16:29:18Z","timestamp":1690388958000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/217\/9\/e20192080\/151858\/Layilin-augments-integrin-activation-to-promote"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,15]]},"references-count":48,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020,9,7]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20192080","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,15]]},"article-number":"e20192080"}}