Universität zu Köln

Arolt, Christoph ORCID: 0000-0002-6366-2285, Meyer, Moritz, Ruesseler, Vanessa, Nachtsheim, Lisa, Wuerdemann, Nora, Dreyer, Thomas, Gattenloehner, Stefan, Wittekindt, Claus, Buettner, Reinhard, Quaas, Alexander and Klussmann, Jens Peter (2020). Lymphocyte activation gene 3 (LAG3) protein expression on tumor-infiltrating lymphocytes in aggressive and TP53-mutated salivary gland carcinomas. Cancer Immunol. Immunother., 69 (7). S. 1363 - 1374. NEW YORK: SPRINGER. ISSN 1432-0851

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Arolt, Christoph UNSPECIFIED orcid.org/0000-0002-6366-2285 UNSPECIFIED Meyer, Moritz UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruesseler, Vanessa UNSPECIFIED UNSPECIFIED UNSPECIFIED Nachtsheim, Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Wuerdemann, Nora UNSPECIFIED UNSPECIFIED UNSPECIFIED Dreyer, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Gattenloehner, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Wittekindt, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Quaas, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Klussmann, Jens Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-340079
DOI:	10.1007/s00262-020-02551-6
Journal or Publication Title:	Cancer Immunol. Immunother.
Volume:	69
Number:	7
Page Range:	S. 1363 - 1374
Date:	2020
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-0851
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language T-CELLS; TP53 MUTATION; P53; PATTERNS; IMMUNITY; PD-L2 Multiple languages Oncology; Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/34007