Prognostic role of PD-L1 and immune-related gene expression profiles in giant cell tumors of bone

Metović, Jasna; Annaratone, Laura; Linari, Alessandra; Osella‐Abate, Simona; Musuraca, Chiara; Veneziano, Francesca; Vignale, Chiara; Bertero, Luca; Cassoni, Paola; Ratto, Nicola; Comandone, Alessandro; Grignani, Giovanni; Piana, Raimondo; Papotti, Mauro

doi:10.1007/s00262-020-02594-9

Cited by 8 publications

(10 citation statements)

References 48 publications

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“…To understand the tumor microenvironment of GCTB, we established this study to focus on the tumor immune microenvironment of primary lesions and recurrent lesions with and without denosumab therapy in GCTB patients, and to investigate an immune checkpoint inhibitor treatment strategy for GCTB patients. A prior immunohistochemical study showed PD-L1 expression by tumor cells and multinucleated giant cells in 28.3% of GCTB specimens, and this was associated with shortened disease-free survival and high Ki-67 positivity 22 . Moreover, this previous study focused on two immune-related genes, TLR8 and LCK , which are related to innate immunity activation and CD4 + and CD8 + lymphocyte development.…”

Section: Discussionmentioning

confidence: 89%

“…Moreover, this previous study focused on two immune-related genes, TLR8 and LCK , which are related to innate immunity activation and CD4 + and CD8 + lymphocyte development. Lower TLR8 and LCK expression were correlated with PD-L1 immunoexpression positivity, but after denosumab treatment, TLR8 and LCK expression increased 22 . Our results showed PD-L1 immunoexpression in about 28% of primary specimens without denosumab treatment, and this was significantly related to shortened recurrence-free survival.…”

Section: Discussionmentioning

confidence: 89%

“…Several investigations and clinical trials concerning the PD-L1/PD-1 axis have been developed for various cancers, including malignant bone tumors 16 – 21 . Metovic et al investigated PD-L1 expression in GCTB patients and reported that PD-L1 expression was correlated with shorter disease-free survival 22 .…”

Section: Introductionmentioning

confidence: 99%

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Tumor microenvironment in giant cell tumor of bone: evaluation of PD-L1 expression and SIRPα infiltration after denosumab treatment

Toda

Kohashi

Yamamoto

et al. 2021

Sci Rep

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Giant cell tumor of bone (GCTB) is an intermediate malignant bone tumor that is locally aggressive and rarely metastasizes. Denosumab, which is a receptor activator of nuclear factor kappa B ligand (RANKL) inhibitor, can be used to treat GCTB. We focused on potential immunotherapy for GCTB and investigated the tumor microenvironment of GCTB. Programmed death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) expression and signal-regulatory protein alpha (SIRPα), forkhead box P3 (FOXP3), and cluster of differentiation 8 (CD8) infiltration were assessed by immunohistochemical studies of 137 tumor tissues from 96 patients. Of the naive primary specimens, 28% exhibited PD-L1 expression and 39% exhibited IDO1 expression. There was significantly more SIRPα+, FOXP3+, and CD8+ cell infiltration in PD-L1- and IDO1-positive tumors than in PD-L1- and IDO1-negative tumors. The frequency of PD-L1 expression and SIRPα+ cell infiltration in recurrent lesions treated with denosumab was significantly higher than in primary lesions and recurrent lesions not treated with denosumab. PD-L1 expression and higher SIRPα+ cell infiltration were significantly correlated with shorter recurrence-free survival. PD-L1 and SIRPα immune checkpoint inhibitors may provide clinical benefit in GCTB patients with recurrent lesions after denosumab therapy.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 89%

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Tumor microenvironment in giant cell tumor of bone: evaluation of PD-L1 expression and SIRPα infiltration after denosumab treatment

Toda

Kohashi

Yamamoto

et al. 2021

Sci Rep

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“…The interaction of PD-1/PD-L1 plays important roles in the maintenance of immunological tolerance and in modulating the immune response [ 31 ]. Emerging evidence has revealed that the expression of PD-L1 on tumor cells leads to immunosuppression and consequently enhances aggressiveness [ 19 , 32 ]. Therefore, PD-L1 expression has been considered a potential biomarker for the response to anti-PD-1/PD-L1 agents in various tumors [ 11 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

The miR-199a-5p/PD-L1 axis regulates cell proliferation, migration and invasion in follicular thyroid carcinoma

et al. 2022

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Background Follicular thyroid carcinoma (FTC) is the second most common cancer of the thyroid and easily develops into distant metastasis. PD-L1 is known to be associated with the carcinogenesis and progression of thyroid carcinoma. Our study aimed to investigate the biological functions of PD-L1 and to identify miRNAs that were responsible for modulating the activity of PD-L1. Methods A total of 72 patients with FTC at The Second Affiliated Hospital of Fujian Medical University were enrolled in this retrospective study. Immunohistochemical (IHC) assay was used to measure PD-L1 expression in FTC. The association between PD-L1 expression and clinicopathologic characteristics was evaluated. Bioinformatics analysis, RT–qPCR and western blotting were used to examine the relationships between miR-199a-5p, PD-L1 and Claudin-1. Cell proliferation, migration and invasion were evaluated by using CCK8 and Transwell migration and invasion assays. Target prediction and luciferase reporter assays were performed to verify the binding between miR-199a-5p and PD-L1. Rescue assay was performed to confirm whether PD-L1 downregulation abolished the inhibitory effect of miR-199a-5p. Results Among 72 pairs of tumor and normal specimens, the proportion of PD-L1 positive samples was higher in FTC tissues than in normal tissues. The results of ESTIMATE and CIBERSORT illustrated that there was a positive correlation between PD-L1 expression and immune infiltration, especially regulatory T cells and M1 macrophages. Prediction of immunotherapy revealed that patients with high PD-L1 expression might benefit from immune checkpoint inhibitors. Transwell migration and invasion assays showed that PD-L1 downregulation in FTC cells could significantly inhibit cell migration and invasion. The bioinformatics analysis and luciferase activity results indicated that PD-L1 was a potential target of miR-199a-5p. Knockdown of PD-L1 reversed the miR-199a-5p inhibitor mediated promotion effect. In addition, we found that PD-L1 expression was positively correlated with Claudin-1 expression and that miR-199a-5p affected the progression of FTC cells through the negative regulation of PD-L1 and Claudin-1. Conclusions Our study revealed that PD-L1 expression was elevated in FTC and was closely associated with tumor aggressiveness and progression. MiR-199a-5p has a functional role in the progression and metastasis of FTC by regulating PD-L1 and Claudin-1 expression.

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“…A study by Metovic et al on a series of 50 GCTB has demonstrated an association between programmed death-ligand 1 (PD-L1) immune expression in GCTB and a higher risk of recurrence in terms of disease-free interval, suggesting to perform a PD-L1 immunohistochemical evaluation at diagnosis to select GCTB patients who may potentially be considered for anti-PD-1/PD-L1 therapies [ 48 ].…”

Section: Gctb Cytology Histopathogenesis and New Biomarkers In Molecular Targeted Therapy Eramentioning

confidence: 99%

State of the Art and New Concepts in Giant Cell Tumor of Bone: Imaging Features and Tumor Characteristics

Parmeggiani

Miceli

Errani

et al. 2021

Cancers

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Giant cell tumor of bone (GCTB) is classified as an intermediate malignant tumor due to its locally aggressive behavior, burdened by high local recurrence rate. GCTB accounts for about 4–5% of all primary bone tumors and typically arises in the metaphysis and epiphyses of the long tubular bones. Mutation of gene H3F3A is at the basis of GCTB etiopathogenesis, and its immunohistochemical expression is a valuable method for practical diagnosis, even if new biomarkers have been identified for early diagnosis and for potential tumor recurrence prediction. In the era of computer-aided diagnosis, imaging plays a key role in the assessment of GCTB for surgical planning, patients’ prognosis prediction and post treatment evaluation. Cystic changes, penetrating irregular margins and adjacent soft tissue invasion on preoperative Magnetic Resonance Imaging (MRI) have been associated with a higher rate of local recurrence. Distance from the tumor edge to the articular surface and thickness of unaffected cortical bone around the tumor should be evaluated on Computed Tomography (CT) as related to local recurrence. Main features associated with local recurrence after curettage are bone resorption around the graft or cement, soft tissue mass formation and expansile destruction of bone. A denosumab positive response is represented by a peripherical well-defined osteosclerosis around the lesion and intralesional ossification. Radiomics has proved to offer a valuable contribution in aiding GCTB pre-operative diagnosis through clinical-radiomics models based on CT scans and multiparametric MR imaging, possibly guiding the choice of a patient-tailored treatment. Moreover, radiomics models based on texture analysis demonstrated to be a promising alternative solution for the assessment of GCTB response to denosumab both on conventional radiography and CT since the quantitative variation of some radiomics features after therapy has been correlated with tumor response, suggesting they might facilitate disease monitoring during post-denosumab surveillance.

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Prognostic role of PD-L1 and immune-related gene expression profiles in giant cell tumors of bone

Cited by 8 publications

References 48 publications

Tumor microenvironment in giant cell tumor of bone: evaluation of PD-L1 expression and SIRPα infiltration after denosumab treatment

Tumor microenvironment in giant cell tumor of bone: evaluation of PD-L1 expression and SIRPα infiltration after denosumab treatment

The miR-199a-5p/PD-L1 axis regulates cell proliferation, migration and invasion in follicular thyroid carcinoma

State of the Art and New Concepts in Giant Cell Tumor of Bone: Imaging Features and Tumor Characteristics

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