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Mair, Maximilian J.; Kiesel, Barbara; Feldmann, Katharina; Widhalm, Georg; Dieckmann, Karin; Wöhrer, Adelheid; Müllauer, Leonhard; Preusser, Matthias; Berghoff, Anna S.

LAG-3 expression in the inflammatory microenvironment of glioma

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  • Media type: E-Article
  • Title: LAG-3 expression in the inflammatory microenvironment of glioma
  • Contributor: Mair, Maximilian J.; Kiesel, Barbara; Feldmann, Katharina; Widhalm, Georg; Dieckmann, Karin; Wöhrer, Adelheid; Müllauer, Leonhard; Preusser, Matthias; Berghoff, Anna S.
  • imprint: Springer Science and Business Media LLC, 2021
  • Published in: Journal of Neuro-Oncology
  • Language: English
  • DOI: 10.1007/s11060-021-03721-x
  • ISSN: 0167-594X; 1573-7373
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:sec> <jats:title>Purpose</jats:title> <jats:p>Immune modulatory therapies including immune checkpoint inhibitors have so far failed to result in clinically meaningful efficacy in glioma. We aimed to investigate lymphocyte activation gene 3 (LAG-3), an inhibitory receptor on immune cells and target of second-generation immune checkpoint inhibitors, in glioma.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>97 patients with diffuse glioma (68 with glioblastoma, 29 with WHO grade II-III glioma) were identified from the Neuro-Biobank of the Medical University of Vienna. LAG-3 expression in the inflammatory microenvironment was assessed by immunohistochemistry (monoclonal anti-LAG-3 antibody, clone 17B4) and correlated to CD3+ , CD8+ , CD20+ and PD-1+ tumor-infiltrating lymphocytes (TILs) and PD-L1 expression on tumor cells.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>LAG-3+ TILs could be observed in 10/97 (10.3%) IDH-wildtype samples and in none of the included IDH-mutant glioma samples (p = 0.057). Further, LAG-3+ TILs were only observed in WHO grade IV glioblastoma, while none of the investigated WHO grade II–III glioma presented with LAG-3+ TILs (p = 0.03). No association of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation and presence of LAG-3+ TILs was observed (p = 0.726). LAG-3 expression was associated with the presence of CD3+ (p = 0.029), CD8+ (p = 0.001), PD-1+ (p &lt; 0.001) TILs and PD-L1+ tumor cells (p = 0.021), respectively. No association of overall survival with LAG-3+ TIL infiltration was evident (median OS 9.9 vs. 14.2 months, p = 0.95).</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>LAG-3 is only rarely expressed on TILs in IDH-wildtype glioma and associated with active inflammatory milieu as defined by higher TIL density. Immune microenvironment diversity should be considered in the design of future immunotherapy trials in glioma.</jats:p> </jats:sec>