Journal
CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 69, Issue 9, Pages 1905-1916Publisher
SPRINGER
DOI: 10.1007/s00262-020-02594-9
Keywords
Giant cell tumor of bone; PD-L1; Immune-related genes; NanoString technology; Prognosis
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Funding
- Fondazione per i Tumori muscolo scheletrici, Torino [1704/2018]
- Italian Ministry for Education, University and Research (Ministero dell'Istruzione, dell'Universita e della Ricerca-MIUR) under the program Dipartimenti di Eccellenza 2018-2022 [D15D18000410001]
- Fondazione Umberto Veronesi
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Giant cell tumor of bone (GCTB) is a locally aggressive and rarely metastatic tumor, with a relatively unpredictable clinical course. A retrospective series of 46 GCTB and a control group of 24 aneurysmal bone cysts (ABC) were selected with the aim of investigating the PD-L1 expression levels and immune-related gene expression profile, in correlation with clinicopathological features. PD-L1 and Ki67 were immunohistochemically tested in each case. Furthermore, comprehensive molecular analyses were carried out using NanoString technology and nCounter PanCancer Immune Profiling Panel, and the gene expression results were correlated with clinicopathological characteristics. PD-L1 expression was observed in 13/46 (28.3%) GCTB (and in 1/24, 4.2%, control ABC, only) and associated with a shorter disease free interval according to univariate analysis. Moreover, in PD-L1-positive lesions, three genes (CD27, CD6 and IL10) were significantly upregulated (p < 0.01), while two were downregulated (LCK and TLR8, showing borderline significance, p = 0.06). Interestingly, these genes can be related to maturation and immune tolerance of bone tissue microenvironment, suggesting a more immature/anergic phenotype of giant cell tumors. Our findings suggest that PD-L1 immunoreactivity may help to select GCTB patients with a higher risk of recurrence who could potentially benefit from immune checkpoint blockade.
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