Lymphocyte activation gene 3 (LAG3) protein expression on tumor-infiltrating lymphocytes in aggressive and TP53-mutated salivary gland carcinomas.
Cancer Immunol Immunother
; 69(7): 1363-1373, 2020 Jul.
Article
em En
| MEDLINE
| ID: mdl-32232506
ABSTRACT
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias das Glândulas Salivares
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Biomarcadores Tumorais
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Antígenos CD
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Linfócitos do Interstício Tumoral
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Proteína Supressora de Tumor p53
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Antígenos CD8
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Mutação
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article