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1000 Titel
  • Lymphocyte activation gene 3 (LAG3) protein expression on tumor-infiltrating lymphocytes in aggressive and TP53-mutated salivary gland carcinomas
1000 Autor/in
  1. Arolt, Christoph |
  2. Meyer, Moritz |
  3. Ruesseler, Vanessa |
  4. Nachtsheim, Lisa |
  5. Wuerdemann, Nora |
  6. Dreyer, Thomas |
  7. Gattenlöhner, Stefan |
  8. Wittekindt, Claus |
  9. Buettner, Reinhard |
  10. Quaas, Alexander |
  11. Klussmann, Jens Peter |
1000 Erscheinungsjahr 2020
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-03-30
1000 Erschienen in
1000 Quellenangabe
  • 69(7):1363-1373
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00262-020-02551-6 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370910/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Salivary gland carcinomas (SGCs) are rare and can be subdivided into distinct entities, some of which confer a poor prognosis. As targets for effective systemic therapy are warranted, some studies investigated the role of immune-checkpoint proteins PD-L1 and CTLA-4 in SGC. Our study depicts the expression of lymphocyte activation gene 3 (LAG3) in a test cohort and a larger validation cohort, totaling 139 SGCs. LAG3 is expressed on tumor-infiltrating lymphocytes (TILs), mediates T cell exhaustion and is subject to numerous currently recruiting clinical studies. Overall, one-third of SGCs were infiltrated by LAG3-expressing TILs with a strikingly high concordance between the test cohort and the validation cohort (30% and 28.2%, respectively). In the validation cohort, entity-wise LAG3 expression frequencies were highly variable. The highest rates were observed in salivary duct carcinoma (SDC; 66.7%) and adenocarcinoma not otherwise specified (ANOS; 50.0%). We observed LAG3 expression on effector T cells and in smaller frequencies also on FOXP3- T helper cells and FOXP3+ Tregs. LAG3 expression significantly correlated with advanced nodal metastases, cytotoxic T cell infiltrate and TP53 mutations. In the group of adenoid cystic carcinomas, LAG3 expression was also associated with a shorter event-free survival (EFS). Tumors with TP53 nonsense mutations (TP53 null type) exhibited higher LAG3 frequencies and a shorter EFS compared to TP53 wild type. This is the first report of LAG3 expression in SGC, a promising target for immunotherapy. LAG3 blockage could be distinctly applicable for SDC and ANOS, two SGC types with a particularly poor outcome.
1000 Sacherschließung
lokal Gene Expression Regulation, Neoplastic [MeSH]
lokal Aged [MeSH]
lokal Prognosis
lokal Tumor micro-environment
lokal Original Article
lokal Male [MeSH]
lokal CD8 Antigens/metabolism [MeSH]
lokal Salivary gland carcinoma
lokal Combined Modality Therapy [MeSH]
lokal Biomarkers, Tumor/analysis [MeSH]
lokal LAG3
lokal
lokal Female [MeSH]
lokal Follow-Up Studies [MeSH]
lokal Mutation [MeSH]
lokal Humans [MeSH]
lokal Salivary Gland Neoplasms/metabolism [MeSH]
lokal Retrospective Studies [MeSH]
lokal Salivary Gland Neoplasms/immunology [MeSH]
lokal Tumor Suppressor Protein p53/genetics [MeSH]
lokal Lymphocytes, Tumor-Infiltrating/immunology [MeSH]
lokal Survival Rate [MeSH]
lokal Salivary Gland Neoplasms/genetics [MeSH]
lokal Prognosis [MeSH]
lokal Salivary Gland Neoplasms/pathology [MeSH]
lokal Antigens, CD/metabolism [MeSH]
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0002-6366-2285|https://frl.publisso.de/adhoc/uri/TWV5ZXIsIE1vcml0eg==|https://frl.publisso.de/adhoc/uri/UnVlc3NlbGVyLCBWYW5lc3Nh|https://frl.publisso.de/adhoc/uri/TmFjaHRzaGVpbSwgTGlzYQ==|https://frl.publisso.de/adhoc/uri/V3VlcmRlbWFubiwgTm9yYQ==|https://frl.publisso.de/adhoc/uri/RHJleWVyLCBUaG9tYXM=|https://frl.publisso.de/adhoc/uri/R2F0dGVubMO2aG5lciwgU3RlZmFu|https://frl.publisso.de/adhoc/uri/V2l0dGVraW5kdCwgQ2xhdXM=|https://frl.publisso.de/adhoc/uri/QnVldHRuZXIsIFJlaW5oYXJk|https://frl.publisso.de/adhoc/uri/UXVhYXMsIEFsZXhhbmRlcg==|https://frl.publisso.de/adhoc/uri/S2x1c3NtYW5uLCBKZW5zIFBldGVy
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1000 Erstellt am 2023-11-18T05:43:27.427+0100
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