<i>CD274/PD-L1</i>gene amplification and PD-L1 protein expression are common events in squamous cell carcinoma of the oral cavity

Straub, Melanie; Drecoll, Enken; Pfarr, Nicole; Weichert, Wilko; Langer, Rupert; Hapfelmeier, Alexander; Götz, Carolin; Wolff, Klaus‐Dietrich; Kolk, Andreas; Specht, Katja

doi:10.18632/oncotarget.7593

Cited by 153 publications

(165 citation statements)

References 48 publications

(56 reference statements)

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“…The expression of PD-L1 in this patient was comparable to that in other genitourinary cancer types, such as bladder cancer (20%) (25), and non-genitourinary cancer types, such as breast cancer (23.4%) (26), colorectal cancer (36%) (27), testicular seminomas (73%) (28) and cancer of the oral cavity (73%) (29). The PD-1/PD-L1 axis has a notable role in the immune antitumor response (30,31).…”

Section: Discussionsupporting

confidence: 54%

Clinicopathological analysis of epithelioid inflammatory myofibroblastic sarcoma

Gao

Zhao

et al. 2018

Oncol Lett

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Abstract. Inflammatory myofibroblastic tumor (IMT) is a distinctive neoplasm composed of myofibroblastic and fibroblastic spindle cells, accompanied by the inflammatory infiltration of plasma cells, lymphocytes and/or eosinophils. Epithelioid inflammatory myofibroblastic sarcoma (EIMS), which primarily consists of cells with a round or epithelioid morphology, is associated with a poor prognosis and rapid development of local recurrence, and has been recognized to be a variant of IMT. Diagnosis of EIMS is difficult owing to its close resemblance to malignant mesothelioma, anaplastic large cell lymphoma, gastrointestinal stromal tumor and other malignant diseases. In the present study, a case of this rare tumor was evaluated in a 26-year-old male who was admitted to hospital after experiencing abdominal pain for ~18 days and abdominal distention for 1 week. The patient's tumor was examined by imaging, gross examination, histology, immunohistochemistry and fluorescence in situ hybridization (FISH). The magnetic resonance imaging enhanced-scanning image revealed that the morphology of the tumor was irregular, and signal was medley consisting of high and low hybrid reinforcement. Tumors were located in the bladder and rectal pit, in the lower part of the lower abdomen, indicating the presence of malignancy and involvement of the small intestine and rectum. Enhanced-scanning imaging revealed notable inhomogeneous enhancement. Gross examination revealed that the tumor was solid and had a variegated appearance with alternating fleshy and mucoid areas in the cut surface. Microscopically, the tumors were dominated by sheets of epithelioid-to-round cells with a prominent inflammatory infiltrate. The majority of the stroma was myxoid. Immunohistochemically, the tumor cells exhibited diffuse strong staining for ALK receptor tyrosine kinase (hereafter ALK), vimentin, tumor protein P53, desmin, Wilms' tumor 1 and programmed death-ligand 1. FISH analysis also revealed the existence of ALK rearrangement. The expression of PD-L1 in EIMS indicates that the immune checkpoint blockade could represent a novel therapy for the treatment of EIMS.

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Section: Discussionsupporting

confidence: 54%

Clinicopathological analysis of epithelioid inflammatory myofibroblastic sarcoma

Gao

Zhao

et al. 2018

Oncol Lett

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“…PD-L1 is also over-expressed in cancer cells under the influence of oncogenic mutations, such as Phosphatase and tensin homologue (PTEN) loss or Nucleophosmin-anaplastic lymphoma kinase (NPM/ALK) [28, 29]. Amplification at 9p24.1, where PD-L1 resides, has been associated with PD-L1 up-regulation in squamous cell oral carcinoma [30] and non-small cell lung cancer [31]. The activation of the PI3K pathway in response to PTEN loss in both breast cancers [32] and glioblastomas [28] induces PD-L1 expression.…”

Section: Discussionmentioning

confidence: 99%

Membranous and Cytoplasmic Expression of PD-L1 in Ovarian Cancer Cells

Xie

Huang

et al. 2017

Cell Physiol Biochem

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Background: Expression of programmed death-ligand 1 (PD-L1) on tumor cells represents a powerful immune evasion pathway, but the role of intracellular or cytoplasmic PD-L1 has not been investigated in ovarian cancer cells. Methods: Flow cytometry (FCM), Real-time PCR (qPCR), immunohistochemistry (IHC) and western blot were used to determine the expression of PD-L1 in ovarian cancer cells. The cytokines detected in the tumor or tumor associated macrophage (TAM) were used to treat cancer cells. PD-L1 blockade and silencing were used to elucidate the functional significance of cancer-related PD-L1 expression. Results: Based on the results presented, PD-L1 was found variably expressed in the cytoplasm and the cell surface of both HO8910 and SKOV3 cells. TAM or IFN-γ, TNF-α, IL-10 and IL-6 released from TAM stimulated the expression of PD-L1 at the surface of the cancer cells. The IHC results were consistent with the data in vitro showing infiltration of TAM correlated with membranous PD-L1. The increases of PD-L1 at the surface were not due to a shift in the proportion of surface versus intracellular protein, but the contribution of extracellular signal-regulated kinase (ERK)1/2 and phosphoinositide 3-kinase (PI3K) pathway activation. As a consequence, inducible membranous PD-L1 expression on SKOV3 inhibited CD8⁺ T cell function, and cytoplasmic PD-L1 promoted cancer cell growth. Additionally, in mouse models, both PD-L1 and PD-1 mAb resulted in tumor growth inhibition and demonstrated a potential to decrease the number of PD-1⁺CD8⁺T cells. Conclusion: We conclude that TAM induced PD-L1 on the cancer cells represents an immune evasion mechanism. The observations confirm the therapeutic potential of PD-L1/PD-1 mAb to reactivate anti-tumor immunity in ovarian cancer.

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“…22,23 Recently, it has been shown that ~ 20% of patients with triple-negative breast cancer respond to PD-1 blockade with pembrolizumab. 24 Chromosome 9p24.1 amplification appears to be a recurrent event across several tumour types and further studies will need to be performed to assess its value as a biomarker for response to PD-1 blockade.…”

Section: Discussionmentioning

confidence: 99%

Metastatic basal cell carcinoma with amplification of PD-L1: exceptional response to anti-PD1 therapy

et al. 2016

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Metastatic basal cell carcinomas are rare malignancies harbouring Hedgehog pathway alterations targetable by SMO antagonists (vismodegib/sonidegib). We describe, for the first time, the molecular genetics and response of a patient with Hedgehog inhibitor-resistant metastatic basal cell carcinoma who achieved rapid tumour regression (ongoing near complete remission at 4 months) with nivolumab (anti-PD1 antibody). He had multiple hallmarks of anti-PD1 responsiveness including high mutational burden (> 50 mutations per megabase; 19 functional alterations in tissue next-generation sequencing (NGS; 315 genes)) as well as PDL1/PDL2/JAK2 amplification (as determined by both tissue NGS and by analysis of plasma-derived cell-free DNA). The latter was performed using technology originally developed for the genome-wide detection of sub-chromosomal copy-number alterations (CNAs) in noninvasive prenatal testing and showed numerous CNAs including amplification of the 9p24.3-9p22.2 region containing PD-L1, PD-L2 and JAK2. Of interest, PD-L1, PD-L2 and JAK2 amplification is a characteristic of Hodgkin lymphoma, which is exquisitely sensitive to nivolumab. In conclusion, selected SMO antagonist-resistant metastatic basal cell carcinomas may respond to nivolumab based on underlying molecular genetic mechanisms that include PD-L1 amplification and high tumour mutational burden.

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CD274/PD-L1gene amplification and PD-L1 protein expression are common events in squamous cell carcinoma of the oral cavity

Cited by 153 publications

References 48 publications

Clinicopathological analysis of epithelioid inflammatory myofibroblastic sarcoma

Clinicopathological analysis of epithelioid inflammatory myofibroblastic sarcoma

Membranous and Cytoplasmic Expression of PD-L1 in Ovarian Cancer Cells

Metastatic basal cell carcinoma with amplification of PD-L1: exceptional response to anti-PD1 therapy

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