Journal article

Publication year: 2021

Journal: International Journal of Molecular Sciences

Volume number: 22

Issue number: 1

ISSN: 1661-6596

eISSN: 1422-0067

Open access status: Gold

DOI Link: https://doi.org/10.3390/ijms22010379

Publisher: MDPI

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.

Harvard Citation style: Wuerdemann, N., Puetz, K., Eckel, H., Jain, R., Wittekindt, C., Huebbers, C., et al. (2021) LAG-3, TIM-3 and VISTA Expression on Tumor-Infiltrating Lymphocytes in Oropharyngeal Squamous Cell Carcinoma-Potential Biomarkers for Targeted Therapy Concepts, International Journal of Molecular Sciences, 22(1), Article 379. https://doi.org/10.3390/ijms22010379

APA Citation style: Wuerdemann, N., Puetz, K., Eckel, H., Jain, R., Wittekindt, C., Huebbers, C., Sharma, S., Langer, C., Gattenloehner, S., Buettner, R., Speel, E., Suchan, M., Wagner, S., Quaas, A., & Klussmann, J. (2021). LAG-3, TIM-3 and VISTA Expression on Tumor-Infiltrating Lymphocytes in Oropharyngeal Squamous Cell Carcinoma-Potential Biomarkers for Targeted Therapy Concepts. International Journal of Molecular Sciences. 22(1), Article 379. https://doi.org/10.3390/ijms22010379