Lymphocyte activation gene 3 (LAG3) protein expression on tumor-infiltrating lymphocytes in aggressive and TP53-mutated salivary gland carcinomas.
Aged
Antigens, CD
/ metabolism
Biomarkers, Tumor
/ analysis
CD8 Antigens
/ metabolism
Combined Modality Therapy
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Humans
Lymphocytes, Tumor-Infiltrating
/ immunology
Male
Mutation
Prognosis
Retrospective Studies
Salivary Gland Neoplasms
/ genetics
Survival Rate
Tumor Suppressor Protein p53
/ genetics
Lymphocyte Activation Gene 3 Protein
LAG3
Prognosis
Salivary gland carcinoma
TP53
Tumor micro-environment
Journal
Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732
Informations de publication
Date de publication:
Jul 2020
Jul 2020
Historique:
received:
24
08
2019
accepted:
17
03
2020
pubmed:
2
4
2020
medline:
1
7
2020
entrez:
2
4
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32232506
doi: 10.1007/s00262-020-02551-6
pii: 10.1007/s00262-020-02551-6
pmc: PMC7370910
doi:
Substances chimiques
Antigens, CD
0
Biomarkers, Tumor
0
CD8 Antigens
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Lymphocyte Activation Gene 3 Protein
0
Lag3 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1363-1373Références
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