{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:23:24Z","timestamp":1786116204257,"version":"build-2736575974"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":23,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI046709"],"award-info":[{"award-number":["R01AI046709"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI173163"],"award-info":[{"award-number":["R01AI173163"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F31DE032593"],"award-info":[{"award-number":["F31DE032593"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Brown University Presidential Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Transformed cells frequently adapt to immune pressure by modulating expression of ligands for PD-1 and CTLA-4. Despite the success of therapies targeting these interactions, only a minority of patients experience a clinical response, highlighting the critical need for alternative targets. Prior work from our group showed that the inhibitory receptor KLRG1 binds to tumor-derived E-cadherin. However, the therapeutic potential of targeting KLRG1 signaling remains incompletely understood. To address this, we generated a library of cancer cell lines engineered to express varying levels of E-cadherin. Across multiple models, we demonstrate that E-cadherin expression renders tumors more aggressive in vivo. Using an RMA-S cell line possessing a mutated E-cadherin that abrogates KLRG1 binding while preserving cadherin homotypic interactions, we demonstrate that the protumor effect of E-cadherin expression is largely mediated by KLRG1. To further dissect the cellular targets of KLRG1 signaling, we generated KLRG1fl\/fl mice and performed lineage-specific deletion. Surprisingly, we discovered that KLRG1 expression on CD8+ T cells, rather than on natural killer cells, impairs the immune control of B16-F10 E-cadherin+ tumors. Taken together, these results reveal an underappreciated protumor role for E-cadherin and highlight KLRG1 as a promising target for future checkpoint blockade strategies, particularly in tumors retaining epithelial features.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag046","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T19:37:35Z","timestamp":1777059455000},"source":"Crossref","is-referenced-by-count":0,"title":["E-cadherin expression promotes tumor growth via KLRG1-dependent pathways"],"prefix":"10.1093","volume":"215","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4166-2356","authenticated-orcid":false,"given":"Jacob A","family":"Myers","sequence":"first","affiliation":[{"name":"Division of Biology and Medicine, Department of Molecular Microbiology and Immunology, Brown University , Providence, RI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander R D","family":"Jordon","sequence":"additional","affiliation":[{"name":"Division of Biology and Medicine, Department of Molecular Microbiology and Immunology, Brown University , Providence, RI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4960-131X","authenticated-orcid":false,"given":"Samantha M","family":"Borys","sequence":"additional","affiliation":[{"name":"Division of Biology and Medicine, Department of Molecular Microbiology and Immunology, Brown University , Providence, RI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6108-4147","authenticated-orcid":false,"given":"KhanhLinh","family":"Dinh","sequence":"additional","affiliation":[{"name":"Division of Biology and Medicine, Department of Molecular Microbiology and Immunology, Brown University , Providence, RI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7497-8488","authenticated-orcid":false,"given":"Laurent","family":"Brossay","sequence":"additional","affiliation":[{"name":"Division of Biology and Medicine, Department of Molecular Microbiology and Immunology, Brown University , Providence, RI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"2026080604013930800_vkag046-B1","doi-asserted-by":"crossref","first-page":"8263","DOI":"10.1073\/pnas.91.17.8263","article-title":"E-cadherin null mutant embryos fail to form a trophectoderm epithelium","volume":"91","author":"Larue","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026080604013930800_vkag046-B2","doi-asserted-by":"crossref","first-page":"4435","DOI":"10.1007\/s00018-021-03815-9","article-title":"Cadherins in early neural 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