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Lymphocyte activation gene 3 (LAG3) protein expression on tumor-infiltrating lymphocytes in aggressive and TP53-mutated salivary gland carcinomas.
- Source :
-
Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2020 Jul; Vol. 69 (7), pp. 1363-1373. Date of Electronic Publication: 2020 Mar 30. - Publication Year :
- 2020
-
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.
- Subjects :
- Aged
Combined Modality Therapy
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Humans
Male
Prognosis
Retrospective Studies
Salivary Gland Neoplasms genetics
Salivary Gland Neoplasms immunology
Salivary Gland Neoplasms metabolism
Survival Rate
Lymphocyte Activation Gene 3 Protein
Antigens, CD metabolism
Biomarkers, Tumor analysis
CD8 Antigens metabolism
Lymphocytes, Tumor-Infiltrating immunology
Mutation
Salivary Gland Neoplasms pathology
Tumor Suppressor Protein p53 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0851
- Volume :
- 69
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Cancer immunology, immunotherapy : CII
- Publication Type :
- Academic Journal
- Accession number :
- 32232506
- Full Text :
- https://doi.org/10.1007/s00262-020-02551-6