The immunomodulatory protein B7-H4 is overexpressed in breast and ovarian cancers and promotes epithelial cell transformation

Salceda, Susana Alicia; Tang, Tenny; Kmet, Muriel; Munteanu, Andrei; Ghosh, Malavika; Macina, Roberto A.; Liu, Wenhui; Pilkington, Glenn; Papkoff, Jackie

doi:10.1016/j.yexcr.2005.01.018

Cited by 189 publications

(187 citation statements)

References 34 publications

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“…In the context of malignancy, the precise physiologic and pathologic role of B7-H3 expression has yet to be fully elucidated. Transfection of B7-H3 into experimental tumor lines (P815 mastocytoma, Colon-26, and EL-4 lymphoma) has been reported to accelerate in vivo tumor rejection, supporting a net (22,25), uterus (26), and kidney (27). Krambeck et al (27) recently evaluated B7x in 259 patients with renal cell carcinoma, demonstrating that tumor expression of B7x was associated with adverse pathologic features (including advanced tumor size, grade, and stage) and an increased risk of death from disease (27).…”

Section: Discussionmentioning

confidence: 92%

“…B7-H3 protein expression has been described in numerous peripheral organs along with human malignancies of the lung, stomach, and prostate (16,20,21). B7x was discovered in 2003, and in contrast to B7-H3, has consistently demonstrated a negative costimulatory mechanism via inhibition of CD4 ϩ and CD8 ϩ T cell proliferation, cell-cycle progression, IL-2 production, and rendering tumor cells refractory to apoptosis (8)(9)(10)22). Similar to B7-H3, B7x is a type I transmembrane protein and has a yet-unidentified counterreceptor.…”

mentioning

confidence: 99%

“…Despite mRNA expression in various human tissues, immunohistochemistry (IHC) for B7x fails to reveal detectable protein expression in any healthy human organs (23). In stark contrast, aberrant expression of B7x has been observed in cancers of the breast (22,24), lung (16), ovary (22,25), uterus (26), and kidney (27). Thus, B7x, and perhaps B7-H3, have been proposed as potential therapeutic targets in human malignancy.…”

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confidence: 99%

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B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome

Zang

Thompson²,

Al‐Ahmadie³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

345

337

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B7-H3 and B7x are recently discovered members of the B7-CD28 family thought to dampen peripheral immune responses via negative costimulation. We evaluated their potential expression in human prostate cancer using a large cohort of patients with 7 years of follow-up. We identified 823 patients with tissue available treated with radical prostatectomy between 1985 and 2003. Immunohistochemistry was performed on tissue microarray sections using anti-B7-H3 and -B7x. The percentage and intensity of immunoreactivity by tumor cells were blindly evaluated by two urological pathologists, and outcome analyses were conducted. Both B7-H3 and B7x were highly expressed; 93% and 99% of tumors had aberrant expression, respectively. The median percentage of tumor cells staining positive was 80% for each molecule. Strong intensity for B7-H3 and B7x was noted in 212 (26%) and 120 (15%) patients, respectively. Patients with strong intensity for B7-H3 and B7x were significantly more likely to have disease spread at time of surgery (P < 0.001 and P ‫؍‬ 0.005, respectively). Additionally, patients with strong intensity for B7-H3 and B7x were at significantly increased risk of clinical cancer recurrence (P < 0.001 and P ‫؍‬ 0.005) and cancer-specific death (P ‫؍‬ 0.004 and P ‫؍‬ 0.04, respectively). To our knowledge, we present the largest investigation of B7 family molecules in a human malignancy and a previously undescribed evaluation of B7x in prostate cancer. B7-H3 and B7x are abundantly expressed in prostate cancer and associated with disease spread and poor outcome. Given the proposed immune-inhibitory mechanisms of B7-H3 and B7x, these molecules represent attractive targets for therapeutic manipulation in prostate cancer.immune tolerance ͉ prostatic neoplasms ͉ treatment outcome ͉ biological tumor markers

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Section: Discussionmentioning

confidence: 92%

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confidence: 99%

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confidence: 99%

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B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome

Zang

Thompson²,

Al‐Ahmadie³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

345

337

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“…Although B7-H4 mRNA has been noted in a number of nonlymphoid organs (3), it was originally believed that protein expression was restricted to activated lymphoid cells (4,6,7). Recent reports, however, indicate focal and infrequent protein expression in certain somatic tissues, including distal convoluted tubules of the kidney, ductal and acinar cells of the pancreas, endometrial glands, transitional epithelia of the ureter and bladder, bronchial epithelium of the lung, and columnar epithelium of the gallbladder (5).…”

Section: Discussionmentioning

confidence: 99%

“…Weak or sporadic expression of B7-H4 has also been observed in some peripheral tissues, presumably surveyed from human autopsy specimens or tissues that were removed because of pathologic conditions not directly involving the organ being examined (5). Human cancers of the lung, breast, and ovary have also been shown to aberrantly overexpress the B7-H4 protein ligand (4,6,7).…”

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confidence: 99%

B7-H4 expression in renal cell carcinoma and tumor vasculature: Associations with cancer progression and survival

Krambeck¹,

Thompson²,

Dong³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

279

251

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B7-H4 is a recently described B7 family coregulatory ligand that has been implicated as an inhibitor of T cell-mediated immunity. Although expression of B7-H4 is typically limited to lymphoid cells, aberrant B7-H4 expression has also been reported in several human malignancies. To date, associations of B7-H4 with clinical outcomes for cancer patients are lacking. Therefore, we examined B7-H4 expression in fresh-frozen tumor specimens from 259 renal cell carcinoma (RCC) patients treated with nephrectomy between 2000 and 2003 and performed correlative outcome analyses. We report that 153 (59.1%) RCC tumor specimens exhibited B7-H4 staining and that tumor cell B7-H4 expression was associated with adverse clinical and pathologic features, including constitutional symptoms, tumor necrosis, and advanced tumor size, stage, and grade. Patients with tumors expressing B7-H4 were also three times more likely to die from RCC compared with patients lacking B7-H4 (risk ratio ‫؍‬ 3.05; 95% confidence interval ‫؍‬ 1.51-6.14; P ‫؍‬ 0.002). Additionally, 211 (81.5%) specimens exhibited tumor vasculature endothelial B7-H4 expression, whereas only 6.5% of normal adjacent renal tissue vessels exhibited endothelial B7-H4 staining. Based on these findings, we conclude that B7-H4 has the potential to be a useful prognostic marker for patients with RCC. In addition, B7-H4 represents a target for attacking tumor cells as well as tumor neovasculature to facilitate immunotherapeutic treatment of RCC tumors. Last, we demonstrate that patients with RCC tumors expressing both B7-H4 and B7-H1 are at an even greater risk of death from RCC.B7-H1 ͉ costimulation ͉ tumor biomarker ͉ immunotherapy ͉ kidney neoplasms

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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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The immunomodulatory protein B7-H4 is overexpressed in breast and ovarian cancers and promotes epithelial cell transformation

Cited by 189 publications

References 34 publications

B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome

B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome

B7-H4 expression in renal cell carcinoma and tumor vasculature: Associations with cancer progression and survival

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

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