Clinicopathological and Prognostic Characteristics of CD276 (B7-H3) Expression in Adrenocortical Carcinoma

Liang, Jiayu; Liu, Zhihong; Pei, Tianjiao; Yu, Xiao; Liang, Zhongxing; Tang, Yefeng; Zhou, Chuan; Wu, Kan; Wang, Xianding; Zhang, Fan; Yin, Xiaoxue; Chen, Ni; Wei, Xin; Lu, Yiping; Zhu, Ye

doi:10.1155/2020/5354825

Cited by 14 publications

(9 citation statements)

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“…In agreement with recent findings showing that 90% of ACC samples (n = 48) were positive for B7-H3 ( CD276 ) in immunohistochemical assays ( 60 )⁠, our analysis demonstrated that CD276 overexpression was detected in both LSP and HSP. Remarkably, its expression was considered high in a pan-cancer comparison of most ACC patients ( Figure 7B ).…”

Section: Discussionsupporting

confidence: 93%

Adrenocortical Carcinoma Steroid Profiles: In Silico Pan-Cancer Analysis of TCGA Data Uncovers Immunotherapy Targets for Potential Improved Outcomes

et al. 2021

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Despite progress in understanding the biology of adrenocortical carcinoma (ACC), treatment options have not dramatically changed in the last three decades, nor have we learned how to avoid some of its long-term side effects. Our goal was to improve the understanding of immune pathways that may include druggable targets to enhance immune responses of patients with ACC, focusing on immune evasion and the activation of immune cells against ACC. Our strategy was aimed at improving insight regarding gene expression without steroid interference. Using approaches based on high and low steroid phenotypes (HSP and LSP, respectively), we characterized immune pathways using The Cancer Genome Atlas (TCGA) ACC cohort data. Although previous studies have suggested that patients with ACC receive minimal benefit from immunotherapy, high expression of immune modulators was noted in patients with LSP, suggesting the activation of these biomarkers may be an important adjuvant therapy target after clearance of excess glucocorticoids. In addition, patients with LSP ACC had higher immune cell infiltration than patients with HSP ACC and other cancer subtypes. Our findings can be summarized as follows (1): we confirmed and improved the definition of two immune response pathways to ACC (HSP and LSP) based on in silico transcriptome analysis (2), we demonstrated the steroid profile should be considered, otherwise analyses of ACC immune characteristics can generate confounding results (3), among the overexpressed immunotherapy targets, we demonstrated that LSP was rich in PDCD1LG2 (PD-L2) and both HSP and LSP overexpressed CD276 (B7-H3), which was associated with resistance to anti-PD1 therapy and may have accounted for the modest results of previous clinical trials, and (4) identification of patients with LSP or HSP ACC can be used to help determine whether immunotherapy should be used. In conclusion, we highlighted the differences between LSP and HSP, drawing attention to potential therapeutic targets (CD276, PDCD1, and PDCD1LG2). Treatments to reduce immune evasion, as well as the use of other natural and pharmacological immune activators, should include prior pharmacological inhibition of steroidogenesis. Attempts to combine these with tumor cell proliferation inhibitors, if they do not affect cells of the immune system, may produce interesting results.

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Section: Discussionsupporting

confidence: 93%

Adrenocortical Carcinoma Steroid Profiles: In Silico Pan-Cancer Analysis of TCGA Data Uncovers Immunotherapy Targets for Potential Improved Outcomes

et al. 2021

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“…Cytoplasmic CD276 expression is negatively correlated with both the overall survival and disease-free survival of ACC patients. Gene set enrichment analysis demonstrated that CD276 expression is closely related to immune regulation and malignant biological behavior of ACC (24). To give a more intuitive aspect of the expression level of CD276 in malignancies, we performed a pan-cancer analysis to evaluate CD276 expression level in multiple cancers on UALCAN database (http://ualcan.path.uab.edu/index.html).…”

Section: Expression and Regulation Of Cd276 In Tumor Expression Levelmentioning

confidence: 99%

Section: Expression and Regulation Of Cd276 In Tumormentioning

confidence: 99%

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The Role of CD276 in Cancers

et al. 2021

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ObjectiveAberrant expression of the immune checkpoint molecule, CD276, also known as B7-H3, is associated with tumorigenesis. In this review, we aim to comprehensively describe the role of CD276 in malignancies and its potential therapeutic effect.Data SourcesDatabase including PubMed, EMbase, Cochrane Library, CNKI, and Clinical Trails.gov were searched for eligible studies and reviews. Study selection: Original studies and review articles on the topic of CD276 in tumors were retrieved.ResultsCD276 is an immune checkpoint molecule in the epithelial mesenchymal transition (EMT) pathway. In this review, we evaluated the available evidence on the expression and regulation of CD276. We also assessed the role of CD276 within the immune micro-environment, effect on tumor progression, and the potential therapeutic effect of CD276 targeted therapy for malignancies.ConclusionCD276 plays an essential role in cell proliferation, invasion, and migration in malignancies. Results from most recent studies indicate CD276 could be a promising therapeutic target for malignant tumors.

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“…The results of this study showed that >90% of the samples expressed CD276, and more than half of the samples showed moderate to strong expression. Furthermore, higher intensity of CD276 in tumor cells correlated with increased recurrence risk and overall worse prognosis, while at the same time, increased expression of CD276 in tumor vasculature was associated with tumor invasion of adjacent structures and more advanced disease stage [ 36 ].…”

Section: Tumor Immune Microenvironment In Adrenocortical Carcinomamentioning

confidence: 99%

Tumor Microenvironment in Adrenocortical Carcinoma: Barrier to Immunotherapy Success?

Georgantzoglou

Kokkali

Tsourouflis

et al. 2021

Cancers

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Adrenocortical carcinoma is a rare malignancy with aggressive behavior, with up to 40% of patients presenting with metastases at the time of diagnosis. Both conventional chemotherapeutic regimens and novel immunotherapeutic agents, many of which are currently being tested in ongoing clinical trials, have yielded modest results so far, bringing the need for a deeper understanding of adrenal cancer behavior to the forefront. In the recent years, the tumor microenvironment has emerged as a major determinant of cancer response to immunotherapy and an increasing number of studies on other solid tumors have focused on manipulating the microenvironment in the favor of the host and discovering new potential target molecules. In the present review we aim to explore the characteristics of adrenocortical cancer’s microenvironment, highlighting the mechanisms of immune evasion responsible for the modest immunotherapeutic results, and identify novel potential strategies.

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Clinicopathological and Prognostic Characteristics of CD276 (B7-H3) Expression in Adrenocortical Carcinoma

Cited by 14 publications

References 40 publications

Adrenocortical Carcinoma Steroid Profiles: In Silico Pan-Cancer Analysis of TCGA Data Uncovers Immunotherapy Targets for Potential Improved Outcomes

Adrenocortical Carcinoma Steroid Profiles: In Silico Pan-Cancer Analysis of TCGA Data Uncovers Immunotherapy Targets for Potential Improved Outcomes

The Role of CD276 in Cancers

Tumor Microenvironment in Adrenocortical Carcinoma: Barrier to Immunotherapy Success?

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