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Wuerdemann, Nora; Pütz, Katharina; Eckel, Hans; Jain, Rishabh; Wittekindt, Claus; Huebbers, Christian U.; Sharma, Shachi J.; Langer, Christine; Gattenlöhner, Stefan; Büttner, Reinhard; Speel, Ernst-Jan; Suchan, Malte; Wagner, Steffen; Quaas, Alexander; Klussmann, Jens P.

LAG-3, TIM-3 and VISTA Expression on Tumor-Infiltrating Lymphocytes in Oropharyngeal Squamous Cell Carcinoma—Potential Biomarkers for Targeted Therapy Concepts

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  • Media type: E-Article
  • Title: LAG-3, TIM-3 and VISTA Expression on Tumor-Infiltrating Lymphocytes in Oropharyngeal Squamous Cell Carcinoma—Potential Biomarkers for Targeted Therapy Concepts
  • Contributor: Wuerdemann, Nora; Pütz, Katharina; Eckel, Hans; Jain, Rishabh; Wittekindt, Claus; Huebbers, Christian U.; Sharma, Shachi J.; Langer, Christine; Gattenlöhner, Stefan; Büttner, Reinhard; Speel, Ernst-Jan; Suchan, Malte; Wagner, Steffen; Quaas, Alexander; Klussmann, Jens P.
  • Published: MDPI AG, 2020
  • Published in: International Journal of Molecular Sciences, 22 (2020) 1, Seite 379
  • Language: English
  • DOI: 10.3390/ijms22010379
  • ISSN: 1422-0067
  • Keywords: Inorganic Chemistry ; Organic Chemistry ; Physical and Theoretical Chemistry ; Computer Science Applications ; Spectroscopy ; Molecular Biology ; General Medicine ; Catalysis
  • Origination:
  • Footnote:
  • Description: <jats:p>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 &lt; 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 &lt; 0.001, p &lt; 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.</jats:p>
  • Access State: Open Access