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Review
. 2021 Mar 26:11:654684.
doi: 10.3389/fonc.2021.654684. eCollection 2021.

The Role of CD276 in Cancers

Shengzhuo Liu  1   2 , Jiayu Liang  1 , Zhihong Liu  1 , Chi Zhang  1 , Yang Wang  3 , Alice Helen Watson  4 , Chuan Zhou  1 , Fan Zhang  1 , Kan Wu  1 , Fuxun Zhang  1 , Yiping Lu  1 , Xianding Wang  1
Affiliations
Review

The Role of CD276 in Cancers

Shengzhuo Liu et al. Front Oncol. .

Abstract

Objective: Aberrant 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 sources: Database 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.

Results: CD276 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.

Conclusion: CD276 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.

Keywords: B7-H3; CD276; progression; therapeutic target; tumor.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A): CD276 expression level in cancer and corresponding normal tissues. (B–K): The correlation of CD276 expression with survival in cancer patients (p < 0.05).
Figure 2
Figure 2
B7-H3 increases ROS and HIF-1α through B7-H3-induced Nrf2 suppression, SOD1, SOD2, and PRX3 reduction, thus promote aerobic glycolysis in cancer cells, leading to tumor growth. Human cancer immunotherapy strategies targeting B7-H3 including blockade of B7-H3 with blocking monoclonal antibodies (mAbs); B7-H3 specific antibody-dependent cell-mediated cytotoxicity (ADCC); CD3/B7-H3 bispecific antibodies; Small molecule inhibitors; Engineered chimeric antigen receptor (CAR) T cells; combination with other therapies. In T cells, OX40 engagement by OX40L forms a signaling complex with a number of established pro-inflammatory mediators, including AKT, PI3K, NFkB, ERK. Through the PI3K/AKT signaling pathway, the downstream signatures were activated, such as NFkB activation, IL-2 production, mTOR activation, BcLXL activation. As a result, NFkB activation stimulates the expression of chemokines and cytokines, including IL-10. Interestingly, the activation of TGFB1 receptor could simultaneously suppress the maturation of miR-21 and enhance PDCD4 levels. Consequently, the translation of the anti-inflammatory cytokine IL-10 is inhibited. In RCC cells, the TGFBI could participate in the adhesion, migration, and invasion, depending on the inactivation of VHL.
See this image and copyright information in PMC

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