{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T17:12:31Z","timestamp":1784740351674,"version":"3.55.0"},"reference-count":45,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T00:00:00Z","timestamp":1686873600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Although some patients with diffuse large B\u2010cell lymphoma (DLBCL) show a response to immunotherapy, there are still many who do not respond. This suggests that various immune checkpoints are complicatedly intertwined in the composition of the tumor microenvironment of DLBCL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p>To comprehensively understand the expression of various immune checkpoint genes in DLBCL, we performed NanoString assay in 98 patients to investigate 579 genes. In addition, we performed immunohistochemistry for LAG\u20103 and PD\u2010L1 to compare the results with expression in NanoString assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>As a result of hierarchical clustering of NanoString assay, 98 DLBCLs were classified into three tumor immune microenvironment clusters. Most immune checkpoint genes showed the highest expression in cluster A and the lowest in cluster C. However, the expression of <jats:italic>LAG3<\/jats:italic> was the highest in cluster C and the lowest in cluster A, showing an expression pattern opposite to that of other immune checkpoint genes. In Cluster A, the expression of genes related to T\u2010cell activity such as <jats:italic>CD8A<\/jats:italic> and <jats:italic>GZMB<\/jats:italic> was increased. In Cluster C, the expression of genes related to major histocompatibility complex molecules was the highest. Immunohistochemical stains showed modest agreement with the NanoString results but did not help clustering.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results show that the unique expression pattern of <jats:italic>LAG3<\/jats:italic> in DLBCL contrasts with that of other immune checkpoints. We suggest that the combination of anti\u2010PD\u20101\/PD\u2010L1 and anti\u2010LAG\u20103 blockades in the immunotherapy of DLBCL patients can have a synergistic effect, improving the immunotherapy efficacy and outcome in DLBCL patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.6268","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T10:40:41Z","timestamp":1686912041000},"page":"16359-16369","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A unique expression pattern of <scp><i>LAG3<\/i><\/scp> distinct from that of other immune checkpoints in diffuse large B\u2010cell lymphoma"],"prefix":"10.1002","volume":"12","author":[{"given":"Hyunjee","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Pathology Samsung Medical Center, Sungkyunkwan University School of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang 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