{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T22:43:37Z","timestamp":1789425817816,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,6,11]],"date-time":"2020-06-11T00:00:00Z","timestamp":1591833600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cutan Pathol"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Expression of programmed death ligand 1 (PD\u2010L1) by cutaneous squamous cell carcinomas has been shown to correlate with advanced disease and risk of metastasis. Lymphocyte activation gene 3 (LAG\u20103, or CD223) is an inhibitory receptor that interacts with the PD\u2010L1 axis, which has been shown to be a marker of immune exhaustion and a potential immunotherapy target. However, the role of LAG\u20103 in cutaneous squamous cell carcinoma has not been established.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We reviewed 18 cases of locally advanced and\/or metastatic cutaneous squamous cell carcinomas and assessed for PD\u2010L1 expression, presence or absence of tumor\u2010infiltrating lymphocytes (TILs), and expression of LAG\u20103 by TILs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PD\u2010L1 expression was present in 11 of 13 locally advanced primary tumors and 5 of 5 metastases. TILs were present in all 18 tumors, of which 14 cases were positive for LAG\u20103 expression. In positive cases, LAG\u20103 was expressed on average by 32% of TILs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Advanced cutaneous squamous cell carcinomas frequently express PD\u2010L1 and are associated with an inflammatory response. LAG\u20103 expression by TILs was identified in a majority of cases. Our findings suggest that LAG\u20103 positive tumor\u2010associated inflammatory cells may play a role in the development of advanced disease and offer another potential target for drug therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cup.13709","type":"journal-article","created":{"date-parts":[[2020,4,12]],"date-time":"2020-04-12T05:19:04Z","timestamp":1586668744000},"page":"882-887","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["<scp>PD\u2010L1<\/scp> and <scp>LAG<\/scp>\u20103 expression in advanced cutaneous squamous cell carcinomas"],"prefix":"10.1111","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2594-7383","authenticated-orcid":false,"given":"Sam","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Dermatology University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel A.","family":"Slater","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Sayed","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9185-3548","authenticated-orcid":false,"given":"Paul B.","family":"Googe","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of North Carolina  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2017.06.025"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200103293441306"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2015.06.110"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.14694\/EdBook_AM.2014.34.e397"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2018.01.075"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1586\/era.11.36"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(08)70178-5"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1245\/ASO.2006.07.022"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.13508"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2015.4994"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/cup.12728"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2017.05.047"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/DAD.0000000000001164"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3239"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aad7118"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1805131"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1200694"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1501824"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.2147\/ITT.S135639"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12519"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31184"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830241246"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2004.08.010"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxp107"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-1620"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.48.5326"},{"key":"e_1_2_6_28_1","unstructured":"Dako. 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