Immune checkpoint of B7-H3 in cancer: from immunology to clinical immunotherapy

Abstract

Immunotherapy for cancer is a rapidly developing treatment that modifies the immune system and enhances the antitumor immune response. B7-H3 (CD276), a member of the B7 family that plays an immunoregulatory role in the T cell response, has been highlighted as a novel potential target for cancer immunotherapy. B7-H3 has been shown to play an inhibitory role in T cell activation and proliferation, participate in tumor immune evasion and influence both the immune response and tumor behavior through different signaling pathways. B7-H3 expression has been found to be aberrantly upregulated in many different cancer types, and an association between B7-H3 expression and poor prognosis has been established. Immunotherapy targeting B7-H3 through different approaches has been developing rapidly, and many ongoing clinical trials are exploring the safety and efficacy profiles of these therapies in cancer. In this review, we summarize the emerging research on the function and underlying pathways of B7-H3, the expression and roles of B7-H3 in different cancer types, and the advances in B7-H3-targeted therapy. Considering different tumor microenvironment characteristics and results from preclinical models to clinical practice, the research indicates that B7-H3 is a promising target for future immunotherapy, which might eventually contribute to an improvement in cancer immunotherapy that will benefit patients.

Transforming Growth Factor Beta 2 (TGFB2) mRNA Levels, in Conjunction with Interferon-Gamma Receptor Activation of Interferon Regulatory Factor 5 (IRF5) and Expression of CD276/B7-H3, Are Therapeutically Targetable Negative Prognostic Markers in Low-Grade Gliomas

“…CD68 was also found to be a specific marker for macrophages in the inflammatory response and played a crucial role in suppressing T-cell-mediated immunity [ 44 ] ( Figure 1 , Table S1 ). Significant upregulation was observed for the mRNA expression of B7-H3 (CD276), a member of the B7 family that plays an immunoregulatory role in the T-cell response, highlighting this molecule as a novel potential target for cancer immunotherapy [ 45 , 46 ]. Statistical contrast of normal tissue and primary tumor for CD276 mRNA expression in our study showed a significant ( p < 0.0001) 4.03-fold increase in mRNA expression relative to normal tissue ( Figure 1 , Table S1 ).…”

Discovery of immunotherapy targets for pediatric solid and brain tumors by exon-level expression

“…Specifically, FN1 encodes fibronectin which is involved in cell adhesion and migration processes including embryogenesis, wound healing, blood coagulation, host defense, and metastasis 28 . The identified FN1 AS target encodes the alternatively spliced extra domain B of FN1 (EDB) 29 which is highly expressed in all solid and brain tumor types except RB, with the highest prevalence in OS, EWS, RMS, WT, MEL, HGG and EPN (Extended Data 36,37 .…”

Neuroblastoma in the Era of Precision Medicine: A Clinical Review

“…The B7-H3 gene is located on chromosome 15 (15q24.1) and can be expressed as a type I transmembrane glycoprotein. Cancer overexpression of B7-H3 has been associated with worse prognosis and higher recurrence rates [36,[38][39][40]. Three potential B7-H3 counter-receptors have been identified: triggering receptor expressed on myeloid cells (TREM) like transcript 2 (TLT-2), interleukin 20 receptor subunit α (IL20RA), and phospholipase A2 receptor 1 (PLA2R1) [36,41].…”

“…CAR T cells targeting GD2 were safely administered to HRNBL patients without significant toxicity or neuropathic pain. First-generation GD2-CAR T cells showed some anti-tumor effect but were limited by expansion, Multiple newer generations are currently being investigated with varying results [38][39][40]. A recent promising trial of GD2-CAR T cells expressing the inducible caspase 9 suicide gene (GD2-CART01) showed an overall response rate of 63% in heavily pretreated patients with HRNBL [40].…”