Upregulation of the B7/CD28 family member B7-H3 in bladder cancer

Wu, Donghai; Zhang, Zichun; Pan, Huixing; Fan, Yuanfeng; Qü, Ping; Zhou, Jian

doi:10.3892/ol.2014.2828

Cited by 9 publications

(4 citation statements)

References 29 publications

(38 reference statements)

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“…A recent review summarized the expanding repertoire of potential targets for immune modulation in the bladder and pointed out CD276, HHLA2, and VTCN1 as such [15]. Our results corroborate this review as well as previous research showing the CD276 mRNA and protein are expressed in BLCA [16] and contribute to the accumulating evidence of its role in BLCA. CD276 expression promotes invasion and metastasis of urothelial cancer cells in vitro [17], and clinical trials with the anti-CD276 antibody MGA271 [18] are under way (www.clinicaltrials.gov).…”

Section: Discussionsupporting

confidence: 90%

Checkpoint Genes at the Cancer Side of the Immunological Synapse in Bladder Cancer

Dobosz¹,

Stempor

Roszik

et al. 2020

Translational Oncology

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Immune checkpoint inhibitors have revolutionized cancer therapy, but not all cancers respond to the currently available drugs, and even within cancers considered responsive to such modality, response rates range between 15 and 40%, depending on the cancer type, the line of treatment, and yet unknown clinical/molecular factors. Coordinated expression of checkpoint proteins was shown to occur on T cells, probably allowing fine-tuning of the signal transmitted to the cell.We performed a bioinformatic analysis of the expression of putative checkpoint mRNAs at the cancer side of the immunological synapse from the bladder cancer tumorgenome atlas (TCGA) database. Fifteen mRNAs, corresponding to both coinhibitory and costimulatory checkpoints, were shown to be expressed above a designated threshold. Of these, seven mRNAs were found to be coexpressed: CD277, PD-1L, CD48, CD86, galectin-9, TNFRSF14 (HVEM), and CD40. The expression of 2 of these mRNAs—BTN3A1 (CD277) and TNFRSF14 (HVEM)—was positively correlated with overall survival in the TCGA database. All these seven mRNA share putative binding sites of a few transcription factors (TFs). Of these, the expression of the TF BACH-2 was positively correlated with the expression of checkpoint mRNAs from the network. This suggests a joint transcriptional regulation on the expression of checkpoint mRNAs at the bladder tumor side of the immunological synapse.

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Section: Discussionsupporting

confidence: 90%

Checkpoint Genes at the Cancer Side of the Immunological Synapse in Bladder Cancer

Dobosz¹,

Stempor

Roszik

et al. 2020

Translational Oncology

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“…Our previous study revealed that the cancer tissue from hepatocellular carcinoma (HCC) patients exhibited significantly increased levels of B7-H3 (10). B7-H3 has also been reported to be involved in the development of a variety of other solid tumor tissue cancer types, including osteosarcoma, pancreatic cancer, glioma, bladder cancer and non-small cell lung cancer (11)(12)(13)(14)(15), as well as in the development of inflammatory diseases (16).…”

Section: Introductionmentioning

confidence: 99%

Involvement of soluble B7‑H3 in combination with the serum inflammatory cytokines interleukin‑17, ‑8 and ‑6 in the diagnosis of hepatocellular carcinoma

Wang

et al. 2017

Oncol Lett

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Abstract. Previous studies have demonstrated that B7-H3, and the inflammatory cytokines interleukin (IL)-17, IL-8 and IL-6, are involved in the development of a variety of tumors. The objectives of the present study were: i) To investigate the association between soluble B7-H3 (sB7-H3) and cytokine levels of IL-17, IL-8 and IL-6 in the serum of patients with hepatocellular carcinoma (HCC); and ii) to determine their potential value for use in HCC diagnosis. Serum sB7-H3, IL-17, IL-8 and IL-6 levels in the HCC patients and healthy control subjects were measured using ELISA. The accuracy of each of these biomarkers in HCC diagnosis was compared using a receiver operating characteristic curve and the area under the curve (AUC). A logistic regression model was used to investigate the accuracy of diagnosing HCC when evaluated using combined determinations of sB7-H3, IL-17, IL-8 and IL-6 levels. The data demonstrated that serum levels of sB7-H3, IL-17, IL-8 and IL-6 were significantly increased in HCC patients compared with those in the healthy control group. Serum sB7-H3 levels were positively associated with serum IL-17, whereas serum IL-8 levels were negatively correlated with serum IL-17 levels. The AUC values for sB7-H3, IL-17, IL-8 and IL-6 were 83.2, 65.7, 95.3 and 97.0%, respectively, and indicated that all four biomarkers exhibited a statistically significant capacity for diagnosing HCC. Using the logistic regression model, the AUC value, sensitivity and specificity, as determined for the combination of the four biomarkers, were 99.2, 96.67 and 97.14%, respectively. This was significantly greater than that achieved when any single biomarker was used alone in the logistic regression model to assess their accuracy in HCC diagnosis. The optimum cutoff value of the predicted probability obtained by the combination of sB7-H3, IL-17, IL-8 and IL-6 in the regression model was 0.5745. To conclude, the present study revealed that there exists a positive association between serum sB7-H3 and IL-17 levels in HCC patients. Determinations involving the combination of serum sB7-H3, IL-17, IL-8 and IL-6 levels demonstrate great potential for use in HCC diagnosis.

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“…In urothelial cancer of the bladder, preoperative bacillus Calmette-Guerin treatment is associated with B7-H3 overexpression [22]. Subsequent studies on urothelial cell tumors confirmed that B7-H3 overexpression is present in bladder tumors across all pathologic stages [22, 55] and is likely a consequence of increased B7-H3 mRNA expression in urothelial carcinoma cells [56]. …”

Section: New Immune Checkpoints B7-h3 B7x and Hhla2mentioning

confidence: 99%

The expanding repertoire of targets for immune checkpoint inhibition in bladder cancer: What lies beneath the tip of the iceberg, PD-L1

Sankin

Narasimhulu

John

et al. 2018

Urologic Oncology: Seminars and Original Investigations

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Over the last decade, a new understanding of tumor-immune system interplay has been ushered in, lead in large part by the discovery of immune checkpoints mediated through B7-CD28 family interactions. Therapeutic blockade of the PD-L1 immune checkpoint pathway has already shown great success as a cancer immunotherapy for advanced urothelial carcinoma, leading to durable clinical remissions in an otherwise incurable disease. There are newly described members of the B7-CD28 family including B7-H3, B7x, and HHLA2. These ligands are thought to play an essential role in suppressing T-cell response, leading to immune tolerance of tumors. This feature makes them attractive targets for novel immunotherapy treatment paradigms. Here, we review the literature of current strategies and future directions of immune checkpoint blockade therapy for bladder cancer.

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Upregulation of the B7/CD28 family member B7-H3 in bladder cancer

Cited by 9 publications

References 29 publications

Checkpoint Genes at the Cancer Side of the Immunological Synapse in Bladder Cancer

Checkpoint Genes at the Cancer Side of the Immunological Synapse in Bladder Cancer

Involvement of soluble B7‑H3 in combination with the serum inflammatory cytokines interleukin‑17, ‑8 and ‑6 in the diagnosis of hepatocellular carcinoma

The expanding repertoire of targets for immune checkpoint inhibition in bladder cancer: What lies beneath the tip of the iceberg, PD-L1

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