{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T08:15:34Z","timestamp":1780647334980,"version":"3.54.1"},"reference-count":60,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T00:00:00Z","timestamp":1634774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81672668"],"award-info":[{"award-number":["81672668"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81874131"],"award-info":[{"award-number":["81874131"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072996"],"award-info":[{"award-number":["82072996"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Adenoid cystic carcinoma (AdCC) and mucoepidermoid carcinoma (MEC) are the two most frequent malignancies of salivary glands. This study aims to explore the expression and migration of LAG3, TIM3, and A2aR in AdCC and MEC, and the potential relationship with oncogenic signaling molecules and immunosuppressive cytokines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      Custom made human salivary gland tissue microarrays included 81 AdCCs, 52\u00a0MECs, 76 normal salivary glands (NSG), and 14 pleomorphic adenoma (PMA) samples. Immunohistochemical analysis of lymphocyte activation gene 3 (LAG3), T\u2010cell immunoglobulin and mucin domain\u2010containing protein 3 (TIM3), adenosine 2a receptor (A2aR), oncogenic phosphorylated S6\u00a0kinase (p\u2010S6) and ERK\n                      <jats:sub>1\/2<\/jats:sub>\n                      (p\u2010ERK\n                      <jats:sub>1\/2<\/jats:sub>\n                      ), and TGF\u2010\u03b21 was performed with salivary gland tissue microarrays of human samples. The correlation of the immunostaining was analyzed based on a digital pathological system, and data were evaluated by hierarchical cluster. Further in\n                      <jats:italic>vitro<\/jats:italic>\n                      studies of knockdown immune checkpoints LAG3, TIM3, and A2aR were carried out by siRNA transfection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The expression levels of LAG3, TIM3, and A2aR were remarkably increased in AdCC and MEC, compared with NSG and PMA samples, but were independent of pathology grade. They were closely correlated with TGF\u2010\u03b21, slightly related to p\u2010ERK\n                      <jats:sub>1\/2<\/jats:sub>\n                      and p\u2010S6. After the knockdown of immune checkpoints LAG3, TIM3, and A2aR, the migration of SACC\u2010LM cell line was significantly reduced.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results suggested that LAG3, TIM3, and A2aR are overexpressed in AdCC and MEC, may promote migration of SACC\u2010LM cell and correlated with TGF\u2010\u03b21 and oncogenic signaling pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/odi.14045","type":"journal-article","created":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T15:43:11Z","timestamp":1634312591000},"page":"175-187","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Overexpression of LAG3, TIM3, and A2aR in adenoid cystic carcinoma and mucoepidermoid carcinoma"],"prefix":"10.1111","volume":"29","author":[{"given":"Meng\u2010Jie","family":"Zhang","sequence":"first","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei\u2010MOST) &amp; Key Laboratory of Oral Biomedicine Ministry of Education School and Hospital of Stomatology Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong\u2010Cong","family":"Wu","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei\u2010MOST) &amp; Key Laboratory of Oral Biomedicine Ministry of Education School and Hospital of Stomatology Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Wang","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei\u2010MOST) &amp; Key Laboratory of Oral Biomedicine Ministry of Education School and Hospital of Stomatology Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei\u2010Lei","family":"Yang","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei\u2010MOST) &amp; Key Laboratory of Oral Biomedicine Ministry of Education School and Hospital of Stomatology Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0932-8013","authenticated-orcid":false,"given":"Zhi\u2010Jun","family":"Sun","sequence":"additional","affiliation":[{"name":"The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei\u2010MOST) &amp; Key Laboratory of Oral Biomedicine Ministry of Education School and Hospital of Stomatology Wuhan University  Wuhan China"},{"name":"Department of Oral and Maxillofacial Head Neck Oncology School &amp; Hospital of Stomatology Wuhan University  Wuhan 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