B7-H4 expression indicates poor prognosis of oral squamous cell carcinoma

Wu, Lei; Deng, Wei‐Wei; Yu, Guang‐Tao; Mao, Liang; Bu, Lin‐Lin; Ma, Si‐Rui; Liu, Bing; Zhang, Wenfeng; Sun, Zhi‐Jun

doi:10.1007/s00262-016-1867-9

Cited by 64 publications

(54 citation statements)

References 39 publications

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“…In a study regarding uterine cervical cancers, the investigators have lumped adencarcinomas and SCCs as a sinle group with no tumor grading distiction [10]. There is, however, a general agreement that a higher expression of PD-L1 is associated with a poorer prognosis in uterine cervix, endometrium, and head & neck caners [10, 33–35]. …”

Section: Discussionmentioning

confidence: 99%

Programmed death-ligand 1 (PD-L1) is expressed in a significant number of the uterine cervical carcinomas

2017

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BackgroundThe programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) immune regulatory axis has emerged as a promising new target for cancer therapeutics, with lasting responses seen in the treatment of metastatic renal and lung carcinomas, as well as melanomas. As tumor surface expression of PD-L1 has been found to correlate with objective responses to anti-PD-L1 immunotherapies, we investigated the expression of PD-L1 in human cervical tumors and provide an adopted scoring system for the systematic evaluation of PD-L1 staining.MethodsImmunohistochemical staining for PD-L1 expression was performed on a tissue microarray of 101 normal and neoplastic cervical tissues. Neoplastic cores were divided into three groups: squamous cell carcinoma, adenosquamous carcinoma, and endocervical adenocarcinoma. PD-L1 expression was scored based on an adopted scoring system accounting to percentage and intensity of positivity, and results provided alongside available clinical and demographic data.ResultsOverall, PD-L1 was positive in 32 of 93 (34.4%) cervical carcinomas. Subcategorically, PD-L1 was positive in 28 of 74 (37.8%) squamous cell carcinomas, two of seven (28.6%) adenosquamous carcinomas, and two of 12 (16.7%) endocervical adenocarcinomas. It was negative in six benign cervical tissues.ConclusionsThis study shows a significant expression of PD-L1 in 34.4% of cervical carcinomas and no expression of PD-L1 in benign cervical tissues. These findings suggest a role for further investigation of anti-PD-L1/PD-1 immunotherapies in the treatment of PD-L1-positive cervical tumors. In addition, our adopted scoring system will facilitate more systematic correlations between tumor reactivity and response to treatment.

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Section: Discussionmentioning

confidence: 99%

Programmed death-ligand 1 (PD-L1) is expressed in a significant number of the uterine cervical carcinomas

2017

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“…All the HNSCC specimens were made into human HNSCC tissue array, including 97 primary HNSCC cases (Outdo Biotech, Shanghai). The custom made human HNSCC tissue microarrays were used in this study as described previously . The study was performed with the approval of the Institutional Medical Ethics Committee of School and Hospital of Stomatology, Wuhan University (2014LUNSHENZI06, 2016LUNSHENZI62).…”

Section: Methodsmentioning

confidence: 99%

γ‐Secretase inhibitor reduces immunosuppressive cells and enhances tumour immunity in head and neck squamous cell carcinoma

Mao

Zhao

et al. 2017

Intl Journal of Cancer

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Immune evasion is a hallmark feature of cancer, and it plays an important role in tumour initiation and progression. In addition, tumour immune evasion severely hampers the desired antitumour effect in multiple cancers. In this study, we aimed to investigate the role of the Notch pathway in immune evasion in the head and neck squamous cell carcinoma (HNSCC) microenvironment. We first demonstrated that Notch1 signaling was activated in a Tgfbr1/Pten-knockout HNSCC mouse model. Notch signaling inhibition using a γ-secretase inhibitor (GSI-IX, DAPT) decreased tumour burden in the mouse model after prophylactic treatment. In addition, flow cytometry analysis indicated that Notch signaling inhibition reduced the sub-population of myeloid-derived suppressor cells (MDSCs), tumour-associated macrophages (TAMs) and regulatory T cells (Tregs), as well as immune checkpoint molecules (PD1, CTLA4, TIM3 and LAG3), in the circulation and in the tumour. Immunohistochemistry (IHC) of human HNSCC tissues demonstrated that elevation of the Notch1 downstream target HES1 was correlated with MDSC, TAM and Treg markers and with immune checkpoint molecules. These results suggest that modulating the Notch signaling pathway may decrease MDSCs, TAMs, Tregs and immune checkpoint molecules in HNSCC.

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“…As members of B7 family, higher B7-H1 expression in human cancer tissues of [51] renal cell carcinoma [52] ovarian cancer [53] non-small cell lung cancer [41], esophageal cancer [54], malignant pleural mesothelioma [55] and colorectal carcinoma [56] is significantly correlated with poor prognosis, while in breast cancer [57], non-small cell lung cancer [58], ovarian cancer [59], renal cell carcinoma [60], pancreatic cancer [26], oral squamous cell carcinoma [61], cholangiocarcinoma [62], hepatocellular carcinoma [63] and esophageal squamous cell carcinoma [64], aberrant expression of B7-H4 has been demonstrated to be associated with a poor clinical outcome. Therefore, we conclude that B7 family members play similar role as negative prognostic factors in tumor development.…”

Section: Discussionmentioning

confidence: 99%

B7-H3 Overexpression Predicts Poor Survival of Cancer Patients: A Meta-Analysis

Zheng

et al. 2016

Cell Physiol Biochem

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Background: B7-H3 exhibits altered expression in various cancers. However, the correlation between B7-H3 expression and prognosis of cancer patients remains controversial. Therefore, we elicit a meta-analysis to investigate the potential value of B7-H3 in the prognostic prediction in human cancers. Materials and Methods: We searched PubMed (last update by June 15th, 2016) to identify studies assessing the effect of B7-H3 on survival of cancer patients. Hazard ratios (HRs) for overall survival (OS), recurrence free survival (RFS) and progression-free survival (PFS) from individual studies were calculated and pooled by using a random-effect or fix-effect model, and heterogeneity and publication bias analyses were also performed. Results: Data from 24 observational studies consisting of 4141 patients were summarized. An elevated baseline B7-H3 was significantly correlated with poor OS (pooled HR = 2.09; 95% CI =1.60-2.74; P < 0.001). Differences across subgroups of tumor type (P = 0.324), year of publication (P = 0.431), ethnicity (P = 0.940), source of HR (P = 0.145), analysis type (P = 0.178) and sample size (P = 0.909) were not significant. Furthermore, high B7-H3 expression also predicted a significantly poor RFS (pooled HR = 1.39; 95% CI = 1.11-1.75; P = 0.004) but not PFS. Conclusions: This meta-analysis clarifies that elevated B7-H3 expression is significantly associated with poor survival in cancer patients.

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B7-H4 expression indicates poor prognosis of oral squamous cell carcinoma

Cited by 64 publications

References 39 publications

Programmed death-ligand 1 (PD-L1) is expressed in a significant number of the uterine cervical carcinomas

Programmed death-ligand 1 (PD-L1) is expressed in a significant number of the uterine cervical carcinomas

γ‐Secretase inhibitor reduces immunosuppressive cells and enhances tumour immunity in head and neck squamous cell carcinoma

B7-H3 Overexpression Predicts Poor Survival of Cancer Patients: A Meta-Analysis

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