Wuerdemann, Nora, Puetz, Katharina, Eckel, Hans, Jain, Rishabh ORCID: 0000-0001-7526-8149, Wittekindt, Claus, Huebbers, Christian U., Sharma, Shachi J., Langer, Christine, Gattenloehner, Stefan, Buettner, Reinhard, Speel, Ernst-Jan ORCID: 0000-0002-3016-2989, Suchan, Malte, Wagner, Steffen ORCID: 0000-0003-0873-1601, Quaas, Alexander and Klussmann, Jens P. (2021). LAG-3, TIM-3 and VISTA Expression on Tumor-Infiltrating Lymphocytes in Oropharyngeal Squamous Cell Carcinoma-Potential Biomarkers for Targeted Therapy Concepts. Int. J. Mol. Sci., 22 (1). BASEL: MDPI. ISSN 1422-0067

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Abstract

Tumor growth and survival requires a particularly effective immunosuppressant tumor microenvironment (TME) to escape destruction by the immune system. While immunosuppressive checkpoint markers like programmed cell death 1 ligand (PD-L1) are already being targeted in clinical practice, lymphocyte-activation-protein 3 (LAG-3), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) and V-domain Ig suppressor of T cell activation (VISTA) inhibitors are currently under investigation in clinical trials. Reliable findings on the expression status of those immune checkpoint inhibitors on tumor-infiltrating lymphocytes (TILs) in the TME of oropharyngeal squamous cell carcinoma (OPSCC) are lacking. This work aims to describe the expression of LAG-3, TIM-3, and VISTA expression in the TME of OPSCC. We created a tissue microarray of paraffin-embedded tumor tissue of 241 OPSCC. Expression of the immune checkpoint protein LAG-3, TIM-3, and VISTA in OPSCC was evaluated using immunohistochemistry and results were correlated with CD8+ T-cell inflammation and human papillomavirus (HPV)-status. 73 OPSCC stained positive for LAG-3 (31%; HPV+:44%; HPV-:26%, p = 0.006), 122 OPSCC stained positive for TIM-3 (51%; HPV+:70%; HPV-:44%, p < 0.001) and 168 OPSCC (70%; HPV+:75%; HPV-:68%, p = 0.313) for VISTA. CD8+ T-cells were significantly associated with LAG-3, TIM-3 and VISTA expression (p < 0.001, p < 0.001, p = 0.007). Immune checkpoint therapy targeting LAG-3, TIM-3, and/or VISTA could be a promising treatment strategy especially in HPV-related OPSCC. Future clinical trials investigating the efficacy of a checkpoint blockade in consideration of LAG-3, TIM-3, and VISTA expression are required.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Wuerdemann, NoraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Puetz, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eckel, HansUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jain, RishabhUNSPECIFIEDorcid.org/0000-0001-7526-8149UNSPECIFIED
Wittekindt, ClausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huebbers, Christian U.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sharma, Shachi J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Langer, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gattenloehner, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buettner, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Speel, Ernst-JanUNSPECIFIEDorcid.org/0000-0002-3016-2989UNSPECIFIED
Suchan, MalteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, SteffenUNSPECIFIEDorcid.org/0000-0003-0873-1601UNSPECIFIED
Quaas, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klussmann, Jens P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-580332
DOI: 10.3390/ijms22010379
Journal or Publication Title: Int. J. Mol. Sci.
Volume: 22
Number: 1
Date: 2021
Publisher: MDPI
Place of Publication: BASEL
ISSN: 1422-0067
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
Biochemistry & Molecular Biology; Chemistry, MultidisciplinaryMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/58033

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