B7-H4 promotes tumor growth and metastatic progression in lung cancer by impacting cell proliferation and survival

Zhang, Xiuqin; Cai, Liming; Zhang, Guangbo; Yu, Shaohua; Huang, Jianan

doi:10.18632/oncotarget.14475

Cited by 22 publications

(25 citation statements)

References 30 publications

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“…This is in agreement with our previous study in mouse models suggesting that B7-H4 expression by the tumor is important for anti-tumor immunity. 33 This difference from the reported association between B7-H4 expression and worse survival outcomes could be due to our analysis focusing on surface expression of B7-H4, uncoupling the protein's roles in immune cell inhibition through the binding of an unknown receptor [13][14][15] with its potential cellintrinsic roles in tumor cells [46][47][48] but further investigation and a larger sample size is warranted.…”

Section: Discussionmentioning

confidence: 73%

Tumor cell expression of B7-H4 correlates with higher frequencies of tumor-infiltrating APCs and higher CXCL17 expression in human epithelial ovarian cancer

et al. 2019

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B7-H4, an immune suppressive member of the B7 family, is highly expressed in a wide variety of human malignancies making it an attractive immunotherapeutic target. However, the association between B7-H4 expression in the tumor microenvironment and the immune infiltrate has not been comprehensively examined. To evaluate the immune tumor microenvironment, we analyzed epithelial ovarian tumors from 28 patients using flow cytometry, immunohistochemistry, functional, and genomic analyses. We determined B7-H4 expression patterns and compared the immune infiltrates of tumors with high and low surface expression of B7-H4. Frequencies and phenotypes of tumor and immune cells were determined using multiple flow cytometry panels. Immunohistochemistry was used to analyze cellular infiltration and location. Publicly available datasets were interrogated to determine intratumoral cytokine and chemokine expression. We found that B7-H4 was predominantly expressed by tumor cells in the epithelial ovarian tumor microenvironment. Surface expression of B7-H4 on tumor cells was correlated with higher levels of infiltrating mature antigen-presenting cells. Further, expression of CXCL17, a monocyte and dendritic cell chemoattractant, correlated strongly with B7-H4 expression. T cells expressed activation markers, but T cells expressing a combination of markers associated with T cell activation/exhaustion phenotype were not prevalent. Overall, our data suggest that B7-H4 is associated with a pro-inflammatory tumor microenvironment.

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Section: Discussionmentioning

confidence: 73%

Tumor cell expression of B7-H4 correlates with higher frequencies of tumor-infiltrating APCs and higher CXCL17 expression in human epithelial ovarian cancer

et al. 2019

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“…B7-H4 expression is significantly associated with poor outcome in patients with RCC (65), lung cancer (66), CRC (67), cholangiocarcinoma (68), glioma (69), pancreatic cancer (70), oral squamous cell carcinoma (71), esophageal squamous cell carcinoma (72), gallbladder cancer (35), ovarian serous carcinoma (73) and gastric cancer (74). B7-H4 expression in RCC is associated with adverse clinical and pathologic features, including constitutional symptoms, tumor necrosis, and advanced tumor size, stage, and grade.…”

Section: B7-h4mentioning

confidence: 99%

“…B7-H4 in lung cancer promotes tumor cell proliferation, invasion and migration, and cell apoptosis (66). Knockdown of B7-H4 by shRNA is accompanied by a marked increase in Bax and caspase-3/caspase-8, but a decrease in Bcl-2, cyclinD1 and activation of AKT, demonstrating a strong promoting role of B7-H4 in lung tumor growth, progression and metastasis.…”

Section: B7-h4mentioning

confidence: 99%

New B7 Family Checkpoints in Human Cancers

Dong

2017

Molecular Cancer Therapeutics

204

201

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T cells are the main effector cells in immune response against tumors. The activation of T cells is regulated by the innate immune system through positive and negative costimulatory molecules. Targeting immune checkpoint regulators such as programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) has achieved notable benefit in a variety of cancers, which leads to multiple clinical trials with antibodies targeting the other related B7/CD28 family members. Recently five new B7 family ligands, B7-H3, B7-H4, B7-H5, B7-H6 and B7-H7, were identified. Here we review recent understanding of new B7 family checkpoint molecules since they have come to the front of cancer research with the concept that tumor cells exploit them to escape immune surveillance. The aim of this article is to address the structure and expression of the new B7 family molecules as well as their roles in controlling and suppressing immune responses of T cells as well as NK cells. We also discuss clinical significance and contribution of these checkpoint expressions in human cancers.

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“…The expression of B7‐H4 in the cell membrane, cytoplasm, and/or nucleus of tumor cells stimulates proliferation in vitro, promotes G1/S phase transition, and correlates with advanced tumor stage and poor prognosis . Inhibition of B7‐H4 has been shown to limit the growth, migration, and invasive potential of tumor cells through increased apoptosis and cell cycle arrest at G0/G1 . The development of cytotoxicity through the inhibition of B7‐H4 in tumor cells can be further coupled with observations that have shown inverse correlation in the number of TILs with B7‐H4 expression.…”

Section: Emerging Prognostic Biomarkersmentioning

confidence: 88%

Overview of established and emerging immunohistochemical biomarkers and their role in correlative studies in MRI

Alvi

Gupta

Borok

et al. 2019

Magnetic Resonance Imaging

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Clinical practice in radiology and pathology requires professional expertise and many years of training to visually evaluate and interpret abnormal phenotypic features in medical images and tissue sections to generate diagnoses that guide patient management and treatment. Recent advances in digital image analysis methods and machine learning have led to significant interest in extracting additional information from medical and digital whole‐slide images in radiology and pathology, respectively. This has led to significant interest and research in radiomics and pathomics to correlate phenotypic features of disease with image analytics in order to identify image‐based biomarkers. The expanding role of big data in radiology and pathology parallels the development and role of immunohistochemistry (IHC) in the daily practice of pathology. IHC methods were initially developed to provide additional information to help classify tumors and then transformed into an indispensable tool to guide treatment in many types of cancer. IHC markers are used in daily practice to identify specific types of cells and highlight their distributions in tissues in order to distinguish benign from neoplastic cells, determine tumor origin, subclassify neoplasms, and support and confirm diagnoses. In this regard, radiomics, pathomics, and IHC methods are very similar since they enable the extraction of image‐based features to characterize various properties of diseases. Due to the dramatic advancements in recent radiomics research, we provide a brief overview of the role of established and emerging IHC biomarkers in various tumor types that have been correlated with radiologic biomarkers to improve diagnostic accuracy, predict prognosis, guide patient management, and select treatment strategies. Level of Evidence: 5 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:341–354.

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B7-H4 promotes tumor growth and metastatic progression in lung cancer by impacting cell proliferation and survival

Cited by 22 publications

References 30 publications

Tumor cell expression of B7-H4 correlates with higher frequencies of tumor-infiltrating APCs and higher CXCL17 expression in human epithelial ovarian cancer

Tumor cell expression of B7-H4 correlates with higher frequencies of tumor-infiltrating APCs and higher CXCL17 expression in human epithelial ovarian cancer

New B7 Family Checkpoints in Human Cancers

Overview of established and emerging immunohistochemical biomarkers and their role in correlative studies in MRI

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