Affinage

CD276

CD276 antigen · UniProt Q5ZPR3

Length
534 aa
Mass
57.2 kDa
Annotated
2026-06-09
100 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD276 (B7-H3) is a cell-surface immune checkpoint molecule that suppresses antitumor immunity while concurrently driving tumor-intrinsic programs of metabolism, survival, and metastasis (PMID:29530936, PMID:12939639). Tumor-cell B7-H3 restrains CD8+ T-cell and NK-cell effector function: antibody blockade increases tumor-infiltrating CD8+ T cells and restores their cytotoxicity, an effect lost upon CD8+ T-cell depletion and enhanced by dual PD-L1 blockade (PMID:29530936), and its forced expression in mouse tumors mediates regression dependent on both CD8+ T cells and NK cells (PMID:12939639). B7-H3 also reshapes the myeloid compartment, promoting M2 macrophage recruitment and differentiation through tumor-cell CCL2 acting on the CCL2-CCR2 axis (PMID:34799346), and inhibits NK cytotoxicity in EBV-driven nasopharyngeal carcinoma (PMID:36996321). Its expression is tightly controlled at multiple levels: transcriptionally by Sp1 downstream of PTEN/TP53 loss (PMID:37163614), by BRD4 (PMID:30664982), by androgen receptor in prostate cancer (PMID:37452083), by promoter DNA methylation reversed by DNMT inhibition (PMID:37967200), and by lactate-driven H3K18 lactylation recruiting Creb1/Ep300 to its promoter (PMID:39990209); by mTORC1 via S6K-mediated phosphorylation of YY2 (PMID:36869048); post-transcriptionally by SRSF3-dependent exon 4 retention (PMID:32719950); and post-translationally by FUT8-mediated core fucosylation at N104, which prevents HSC70/LAMP2A-mediated chaperone-mediated autophagy degradation (PMID:37537172). Independent of immune modulation, B7-H3 acts as a tumor-cell signaling hub that engages partners including CXCR4 and fibronectin to activate PI3K/AKT signaling driving migration, invasion, EMT, apoptosis resistance, and stemness (PMID:29069741, PMID:35003371, PMID:34431237, PMID:37488673), promotes aerobic glycolysis via HK2 (PMID:30952834), confers chemo- and radioresistance via BRCC3-mediated DNA repair and a KIF15/ERK1/2 axis (PMID:27175567, PMID:33011740), and stimulates angiogenesis through NF-κB/VEGFA and VEGF secretion (PMID:31974361, PMID:31292886). Beyond cancer, B7-H3 is a physiologic regulator of bone and metabolism: it promotes osteoblast differentiation and positively controls osteoclastogenesis by suppressing type-I IFN/IDO signaling (PMID:21893365, PMID:34671026), and sustains oxidative metabolism in adipocyte progenitors such that its loss produces spontaneous obesity in mice (PMID:35476450).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2003 Medium

    Established which immune effectors mediate B7-H3-dependent antitumor activity, defining its immunological function before downstream mechanisms were known.

    Evidence Intratumoral B7-H3 plasmid injection with CD8+ T-cell, NK-cell, and CD4+ T-cell depletion in mouse EL-4 lymphoma

    PMID:12939639

    Open questions at the time
    • Plasmid overexpression context; relationship to endogenous tumor B7-H3 immunosuppression unresolved
    • Receptor on T/NK cells not identified
    • Costimulatory vs coinhibitory role context-dependent
  2. 2011 Medium

    Showed B7-H3 has a non-immune physiologic role by demonstrating membrane B7-H3 stimulation drives osteoblast differentiation and shifts OPG/RANKL balance.

    Evidence Anti-B7-H3 mAb stimulation with B7-H3-Fc competitive blocking in human marrow stromal cells

    PMID:21893365

    Open questions at the time
    • Counter-receptor for membrane B7-H3 unknown
    • Intracellular signaling pathway not defined
    • Antibody agonism may not mimic physiologic ligand
  3. 2016 Medium

    Identified tumor-intrinsic, immune-independent mechanisms of chemoresistance, recasting B7-H3 as a signaling effector inside tumor cells.

    Evidence B7-H3 overexpression/knockdown with PI3K/Akt inhibition (LY294002), BRCC3 siRNA, and DNA comet assays in colorectal cancer cells

    PMID:26787540 PMID:27175567

    Open questions at the time
    • How surface B7-H3 transduces intracellular PI3K/AKT signal unclear
    • No structural basis for signaling
    • Single lineage (CRC)
  4. 2017 Medium

    Demonstrated a direct physical partner (CXCR4) linking B7-H3 to pro-metastatic kinase signaling.

    Evidence Co-immunoprecipitation, immunofluorescence co-localization, and shRNA knockdown with migration/metastasis assays in gastric cancer

    PMID:29069741

    Open questions at the time
    • No reciprocal Co-IP or domain mapping
    • Direct vs complex-mediated interaction unconfirmed
    • Stoichiometry unknown
  5. 2018 Medium

    Defined endogenous tumor B7-H3 as a CD8+ T-cell checkpoint amenable to combination blockade, anchoring its therapeutic rationale.

    Evidence Anti-B7-H3 blocking antibody with CD8+ depletion and PD-L1 co-blockade in a syngeneic murine model

    PMID:29530936

    Open questions at the time
    • T-cell receptor for B7-H3 not identified
    • Single model
    • Molecular signal delivered to T cells unknown
  6. 2019 Medium

    Expanded the tumor-intrinsic repertoire to metabolic reprogramming and angiogenesis, and identified BRD4 as a transcriptional driver.

    Evidence Knockdown/overexpression with HK2 inhibition, NF-κB inhibition and VEGFA rescue, VEGF ELISA, and BET inhibitor/BRD4 knockdown across CRC and pancreatic models

    PMID:30664982 PMID:30952834 PMID:31292886 PMID:31974361

    Open questions at the time
    • Whether glycolytic, angiogenic and transcriptional axes are mechanistically linked unresolved
    • Effects largely correlative across separate single-lab studies
  7. 2020 Medium

    Established post-transcriptional control of B7-H3 by SRSF3 and a radioresistance pathway via KIF15/ERK1/2.

    Evidence RNA immunoprecipitation and minigene exon-retention assays for SRSF3; RNA-seq, KIF15 siRNA/inhibitor SB743921 with in vivo radiation in CRC

    PMID:32719950 PMID:33011740

    Open questions at the time
    • Functional consequence of exon 4 retention on protein not detailed
    • How B7-H3 regulates KIF15 transcription unknown
  8. 2021 Medium

    Resolved the myeloid arm of immunosuppression (CCL2-CCR2-M2) and demonstrated fibronectin as a B7-H3 partner driving PI3K/AKT survival and metastasis signaling.

    Evidence Tumor-cell-specific Cd276 KO with CCL2-CCR2 inhibition in ovarian cancer; Co-IP of B7-H3 with fibronectin and exogenous-FN rescue in gastric and renal carcinoma

    PMID:34431237 PMID:34799346 PMID:35003371

    Open questions at the time
    • Direct binding interface for fibronectin not mapped
    • CCL2 regulation mechanism downstream of B7-H3 not detailed
  9. 2021 Medium

    Extended physiologic roles to bone homeostasis, showing B7-H3 positively controls osteoclastogenesis through suppression of type-I IFN/IDO.

    Evidence Transcriptomics with type-I IFN inhibition and IDO knockdown in human osteoclast precursors

    PMID:34671026

    Open questions at the time
    • Mechanism by which B7-H3 suppresses IFN signaling unknown
    • Reconciliation with osteoblast-promoting role not addressed
  10. 2022 High

    Revealed an organismal metabolic function in adipose progenitors, demonstrating B7-H3 sustains oxidative metabolism with KO mice developing spontaneous obesity.

    Evidence RNA-seq, mitochondrial/metabolic assays, and B7-H3 KO mouse phenotyping in adipocyte progenitors

    PMID:35476450

    Open questions at the time
    • Molecular effector linking B7-H3 to oxidative metabolism unidentified
    • Cell-autonomous vs systemic contribution unclear
  11. 2023 High

    Integrated upstream regulation across transcription (Sp1/PTEN-TP53, methylation), translation/signaling (mTORC1-S6K-YY2), and protein stability (FUT8 fucosylation/CMA), explaining how B7-H3 levels are set.

    Evidence GEMM with Sp1 axis and prostate-specific Cd276 KO; mTORC1/S6K phosphorylation of YY2 with CITE-seq and KO; FUT8 N104 mutagenesis with HSC70 Co-IP and CMA degradation assays; DNMT deletion/decitabine demethylation

    PMID:36869048 PMID:37163614 PMID:37537172 PMID:37967200

    Open questions at the time
    • Crosstalk among these regulatory inputs not integrated
    • Relative contribution of each in different tumor types unknown
  12. 2023 Medium

    Broadened tumor-intrinsic signaling to EMT (PI3K/AKT/SIRT1), stemness (AKT/Nrf2/GSH), and exosome-mediated angiogenesis, and identified viral and AR-dependent expression control.

    Evidence CRISPR KO with LY294002 (EMT); mass spectrometry and AKT/Nrf2 analysis (stemness); exosome uptake and AKT1/mTOR/VEGFA assays; EBV-LMP1/PI3K-AKT-mTOR and PDX/ADT-AR models

    PMID:35029291 PMID:36996321 PMID:37263461 PMID:37452083 PMID:37488673

    Open questions at the time
    • Convergence of multiple AKT-centric phenotypes onto a single mechanism unresolved
    • Many readouts single-lineage and correlative
  13. 2025 Medium

    Connected metabolic state to B7-H3 transcription via lactate-driven histone lactylation, linking the tumor metabolic environment to immune evasion.

    Evidence ChIP for H3K18la/Creb1/Ep300 at the B7-H3 promoter, LDHA knockdown, glycolysis inhibition, and CD8+ T-cell assays in vivo

    PMID:39990209

    Open questions at the time
    • Direct causal chain from lactate to promoter occupancy needs orthogonal confirmation
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • The bona fide receptor(s) that B7-H3 engages on T and NK cells to deliver its inhibitory signal remains unidentified, leaving the core mechanism of immune checkpoint function undefined.
  • No counter-receptor identified in the corpus
  • How a cell-surface checkpoint also acts as an intracellular PI3K/AKT signaling node is unresolved
  • No structural model of B7-H3 in ligand/receptor complex

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1430728 Metabolism 3 R-HSA-168256 Immune System 3
Partners
CXCR4FN1FUT8HSPA8LAMP2A

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2023 mTORC1 upregulates B7-H3 (CD276) expression via direct phosphorylation of the transcription factor YY2 by p70 S6 kinase (S6K). B7-H3 deficiency in mTORC1-hyperactive tumors suppresses tumor growth through an immune-mediated mechanism involving increased T-cell activity, IFN-γ responses, and increased tumor cell MHC-II expression, with strikingly increased cytotoxic CD38+CD39+CD4+ T cells. Mechanistic experiments including phosphorylation assays, transcription factor identification, genetic KO models, CITE-seq, and in vivo tumor studies Nature communications High 36869048
2023 FUT8 mediates core fucosylation of CD276 (B7-H3) at N104. FUT8-silence-induced defucosylation at N104 on B7-H3 causes HSC70 (HSPA8) to bind the 106-110 SLRLQ motif of B7-H3, propelling lysosomal proteolysis of B7-H3 through the chaperone-mediated autophagy (CMA) pathway via HSC70/LAMP2A. Mutagenesis, co-immunoprecipitation, lysosomal degradation assays, small-molecule inhibitor (FDW028), in vitro and in vivo tumor models Cell death & disease High 37537172
2025 Lactate-upregulated histone H3K18 lactylation (H3K18la) directly binds to the B7-H3 promoter in conjunction with transcription factor Creb1 and co-activator Ep300, leading to increased B7-H3 expression and tumor immune evasion by reducing CD8+ T cell cytotoxicity. ChIP assay, LDHA knockdown, pharmacological glycolysis inhibition, in vivo tumor models, CD8+ T cell functional assays Theranostics Medium 39990209
2019 B7-H3 promotes aerobic glycolysis and chemoresistance in colorectal cancer cells by upregulating hexokinase 2 (HK2) expression. Depletion of HK2 or treatment with HK2 inhibitors reverses B7-H3-induced glycolysis and chemoresistance. B7-H3 overexpression/knockdown, glucose consumption and lactate production assays, HK2 siRNA and inhibitor experiments, in vitro functional assays Cell death & disease Medium 30952834
2020 B7-H3 promotes colorectal cancer angiogenesis by activating the NF-κB pathway to upregulate VEGFA expression. Conditioned medium from B7-H3 knockdown CRC cells inhibited HUVEC migration, invasion, and tube formation; recombinant VEGFA rescued this effect, and VEGFA siRNA or neutralizing antibody reversed B7-H3 overexpression effects. B7-H3 knockdown/overexpression, conditioned medium experiments on HUVECs, VEGFA siRNA and neutralizing antibody, NF-κB pathway inhibition, in vivo experiments Cell death & disease Medium 31974361
2021 B7-H3 (Cd276) knockout in tumor cells (but not stromal cells) suppresses ovarian cancer progression and reduces M2 macrophage number while increasing IFNγ+CD8+ T cells. B7-H3 expression drives immunosuppression via the CCL2-CCR2-M2 macrophage axis; CCL2 was downregulated in B7-H3 KO tumor cells, and inhibition of CCL2-CCR2 partly negated B7-H3 suppression effects on M2 macrophage migration/differentiation. Syngeneic mouse KO models (tumor cell-specific Cd276 KO), flow cytometry, transcriptome analysis, CCL2-CCR2 axis inhibition experiments Cancer immunology research High 34799346
2023 Loss of PTEN and TP53 induces B7-H3 expression by activating transcription factor Sp1. Prostate-specific deletion of Cd276 in Pten/Trp53 genetically engineered mouse models delayed tumor progression and reversed suppression of tumor-infiltrating T cells and NK cells. Genetically engineered mouse models (GEMM), Sp1 transcription factor experiments, in vivo prostate-specific Cd276 deletion, immune cell phenotyping Science translational medicine High 37163614
2017 B7-H3 promotes gastric cancer cell migration and invasion through interaction with CXCR4. B7-H3 silencing downregulated CXCR4 and inhibited AKT, ERK, and Jak2/Stat3 phosphorylation. Co-immunoprecipitation assays demonstrated a direct protein-protein interaction between B7-H3 and CXCR4, and immunofluorescence confirmed co-localization. shRNA-mediated B7-H3 silencing, co-immunoprecipitation, immunofluorescence co-localization, in vitro migration/invasion assays, in vivo metastasis model (tail vein injection) Oncotarget Medium 29069741
2022 B7-H3 (CD276) is highly expressed in mouse and human adipose tissue, particularly in adipocyte progenitor cells, and is rapidly downregulated upon initiation of adipocyte differentiation. Loss of B7-H3 in progenitors results in impaired oxidative metabolism and increased lipid accumulation. B7-H3 knockout mice develop spontaneous obesity, metabolic dysfunction, and adipose tissue inflammation. RNA sequencing, metabolic studies, B7-H3 KO mouse model, adipocyte differentiation assays, mitochondrial activity measurements Science advances High 35476450
2020 B7-H3 regulates KIF15 expression (independent of NF-κB pathway, as revealed by RNA sequencing), and the B7-H3/KIF15 axis activates ERK1/2 signaling to confer radioresistance in colorectal cancer. siRNA-mediated KIF15 silencing or KIF15 inhibitor SB743921 abolished B7-H3-mediated radioresistance in vitro and in vivo. RNA sequencing, siRNA knockdown, specific KIF15 inhibitor (SB743921), B7-H3 blocking antibody (3E8) in vivo, colony formation assays, cell cycle analysis Cell death & disease Medium 33011740
2016 B7-H3 increases thymidylate synthase (TS) expression via activation of the PI3K/Akt pathway, resulting in colorectal cancer cell resistance to 5-fluorouracil. The PI3K-specific inhibitor LY294002 blocked B7-H3-induced PI3K/Akt activation and TS upregulation. B7-H3 overexpression in SW480 and HCT8 cells, CCK-8 cell viability assays, Western blotting for TS and PI3K/Akt, pharmacological inhibition with LY294002 Tumour biology Medium 26787540
2019 B7-H3 expression in pancreatic cancer is regulated at the transcriptional level by BRD4 (a BET bromodomain protein). BET inhibitors decreased B7-H3 protein and mRNA levels. Furthermore, the BRD4/B7-H3 axis modulates TLR4 expression in pancreatic cancer cells. BET inhibitor drug screening, BRD4 knockdown, RT-PCR and Western blotting for B7-H3 and TLR4, pancreatic cancer cell line experiments The international journal of biochemistry & cell biology Medium 30664982
2016 B7-H3 upregulates BRCC3 (a component of the BRCA1-BRCA2-BRCC3 DNA repair complex) expression, enhancing DNA repair and conferring resistance to 5-fluorouracil-induced DNA damage in colorectal cancer. BRCC3 knockdown in B7-H3-overexpressing cells permitted greater 5-Fu-induced DNA damage. mRNA microarray, RT-PCR, Western blotting, DNA comet assay for DNA damage, siRNA knockdown of BRCC3 in B7-H3 overexpressing cells Oncology reports Medium 27175567
2018 CD276 (B7-H3) knockdown in late endothelial progenitor cells (LEPCs) significantly decreased proliferation and migration while increasing apoptosis. CD276 knockdown caused cell cycle arrest at G0/G1, increased cyclin D2/D3/E1-CDK2/4/6, decreased cyclin A/B-CDK1, decreased pErk1/2 and pAkt. Paradoxically, CD276 KD increased tube formation and angiogenesis in vitro and in vivo, with upregulation of FoxC1/C2 and Hey1/2 (Notch arterial differentiation pathway) and VEGF-VEGFR1 and p-p38. Lentiviral knockdown, FACS cell cycle analysis, tube formation assay in vitro, Matrigel plug angiogenesis assay in vivo, Western blotting for signaling molecules Stem cells Medium 30379377
2021 B7-H3 regulates osteoclast differentiation as a positive physiologic regulator. B7-H3 deficiency inhibits osteoclastogenesis in human osteoclast precursors (OCPs). Mechanistically, B7-H3 inhibition upregulates type-I IFN signaling and IFN-inducible IDO expression; pharmacological inhibition of type-I IFN or IDO knockdown reverses B7-H3-deficiency-mediated osteoclastogenesis suppression. High-throughput transcriptomics, pharmacological inhibition of type-I IFN, IDO knockdown, osteoclast differentiation assays in human OCPs Cell death & disease Medium 34671026
2011 Stimulation of surface B7-H3 on human marrow stromal cells (hMSCs) with a specific anti-B7-H3 monoclonal antibody (4H7) promotes osteoblast differentiation, increasing alkaline phosphatase and osteocalcin markers and mineralized nodule formation. B7-H3 stimulation also increased OPG expression and decreased RANKL expression. This effect was abolished by addition of B7-H3-Fc fusion protein, confirming membrane B7-H3 specificity. Anti-B7-H3 mAb stimulation, B7-H3-Fc competitive blocking, osteoblast differentiation assays (ALP, osteocalcin, mineralized nodule quantification), Western blotting for OPG/RANKL Immunobiology Medium 21893365
2020 SRSF3 splicing factor directly binds to B7-H3 mRNA and contributes to the retention of B7-H3 exon 4, thereby regulating B7-H3 expression in colorectal cancer. RNA immunoprecipitation (RIP) confirmed direct SRSF3-B7-H3 mRNA binding. Knockdown of SRSF3 reduced B7-H3 mRNA and protein, while SRSF3 overexpression increased B7-H3 expression. Individual knockdown of splicing factors, RNA immunoprecipitation (RIP), minigene construct with B7-H3 exons 3-6, qPCR and Western blotting Cancer immunology, immunotherapy Medium 32719950
2023 EBV infection induces B7-H3 expression in nasopharyngeal carcinoma (NPC) via activation of the PI3K/AKT/mTOR signaling pathway through EBV latent membrane protein 1 (LMP1). B7-H3 expression on EBV+ NPC tumor cells negatively correlates with and inhibits NK cell cytotoxic function in vitro and in vivo. EBV infection models, LMP1 expression constructs, PI3K/AKT/mTOR inhibitor experiments, NK cell cytotoxicity assays, NPC xenograft mouse model with adoptive NK cell transfer Cancer immunology research Medium 36996321
2023 CRC-derived exosomal B7-H3 is taken up by human umbilical vein endothelial cells (HUVECs) and activates the AKT1/mTOR/VEGFA signaling pathway, enhancing HUVEC migration, invasion, and tube formation, and promoting pulmonary angiogenesis and CRC metastasis in mice. Exosome isolation and uptake assays, AKT1/mTOR/VEGFA pathway analysis, HUVEC functional assays (migration, invasion, tube formation), in vivo CRC metastasis mouse model Cellular signalling Medium 37263461
2022 B7-H3 promotes EMT in NSCLC by upregulating SIRT1 expression via the PI3K/AKT pathway. CRISPR/Cas9-mediated B7-H3 deletion downregulated SIRT1 and phosphorylated AKT in A549 cells, resulting in increased E-cadherin and decreased N-cadherin and vimentin. PI3K inhibitor LY294002 suppressed SIRT1 expression, placing B7-H3 upstream of PI3K/AKT/SIRT1 in this EMT pathway. CRISPR/Cas9 B7-H3 deletion, SIRT1 siRNA, PI3K inhibitor LY294002, Western blotting for EMT markers and signaling molecules, migration and invasion assays Molecular medicine reports Medium 35029291
2021 B7-H3 inhibits apoptosis in gastric cancer cells through an FN (fibronectin)-dependent pathway. B7-H3 interacts with fibronectin and subsequently activates PI3K/AKT signaling, suppressing pro-apoptotic proteins (Caspase 3, 8, 9, Bax, p53, Apaf-1, Cleaved PARP) and upregulating Bcl-2. shRNA B7-H3 knockdown, bioinformatics correlation (TCGA), co-immunoprecipitation of B7-H3 and fibronectin, apoptosis protein expression by Western blot, exogenous FN rescue experiments Journal of Cancer Medium 35003371
2021 Fibronectin (FN) interacts with B7-H3 in clear cell renal cell carcinoma and promotes tumor metastasis by activating PI3K, AKT, p38, and ERK kinases. B7-H3 knockdown abolished the pro-metastatic effect of exogenous FN, establishing B7-H3 as a required mediator of FN-induced metastasis signaling. B7-H3 knockdown, exogenous FN treatment, co-immunoprecipitation/database correlation for B7-H3-FN interaction, migration/invasion assays, Western blotting for PI3K/AKT/p38/ERK FEBS open bio Medium 34431237
2023 B7-H3 promotes cancer stem cell characteristics in gastric cancer through activation of the AKT/Nrf2/glutathione (GSH) metabolism pathway. B7-H3 knockdown suppressed stemness markers and GSH metabolism; inhibition of AKT signaling suppressed both GSH metabolism and GC stemness. Mass spectrometry identified downregulation of GSH metabolism in shB7-H3 cells. shRNA B7-H3 knockdown, B7-H3 overexpression, mass spectrometry metabolic profiling, Western blotting for AKT/Nrf2, sphere formation assays, multi-color IHC on human tissues, in vivo xenograft Chinese medical journal Medium 37488673
2019 B7-H3 promotes angiogenesis in endothelial cells (HUVECs) through enhancement of VEGF secretion. B7-H3 knockdown decreased HUVEC proliferation, migration, tube formation, and VEGF expression in vitro, and impaired functional vascular network formation in Matrigel plug assays in vivo. B7-H3 transient knockdown in HUVECs, VEGF ELISA, proliferation/migration/tube formation assays, in vivo Matrigel plug assay Immunologic research Medium 31292886
2024 B7-H3 expression in CRPC is negatively regulated by androgen receptor (AR) during the early phase of ADT treatment, but is positively associated with PCa proliferation during subsequent disease progression. These findings were established using patient-derived xenograft (PDX) models longitudinally assessed during post-ADT progression and validated in clinical patient samples. Longitudinal study using PCa patient-derived xenograft (PDX) models with ADT treatment, immunohistochemistry on clinical patient samples Cancer gene therapy Medium 37452083
2023 DNA methylation of the B7-H3 promoter negatively regulates its expression; DNMT inhibition (decitabine) increased B7-H3 expression via demethylation of the B7-H3 locus. This was demonstrated in neuroendocrine prostate cancer and RB1-deficient CRPC models. DNMT gene deletion, decitabine treatment, B7-H3 expression analysis in patient-derived xenograft models, methylation analysis Science translational medicine Medium 37967200
2018 B7-H3 expressed on tumor cells suppresses CD8+ T-cell-mediated immune surveillance. Anti-B7-H3 blockade in a syngeneic murine cancer model increased CD8+ TIL numbers and restored effector function; CD8+ T-cell depletion negated this antitumor efficacy. Dual blockade of B7-H3 and PD-L1 enhanced the antitumor reaction beyond either agent alone. Anti-B7-H3 blocking antibody in syngeneic murine model, CD8+ T-cell depletion experiment, flow cytometry for TIL quantification and function, dual antibody blockade experiment Clinical cancer research Medium 29530936
2003 Mouse B7-H3 mediates antitumor immunity through CD8+ T cells and NK cells (with no contribution from CD4+ T cells). Intratumoral injection of a mouse B7-H3 expression plasmid caused complete regression of 50% of EL-4 lymphoma tumors and generated systemic immunity. CD8+ T cell and NK cell depletion experiments established the cellular requirements for B7-H3-mediated antitumor activity. Intratumoral plasmid injection in mouse EL-4 lymphoma model, immune cell depletion (CD8+ T cell, NK cell, CD4+ T cell), tumor rechallenge to assess systemic immunity Gene therapy Medium 12939639
2021 GM-CSF, enriched in gastric cancer tumor tissue, induces B7-H3 expression on neutrophils via JAK-STAT3 signaling pathway activation, in both time-dependent and dose-dependent manners. Tumor culture supernatant experiments, GM-CSF dose-response and time-course experiments on neutrophils, JAK-STAT3 pathway inhibition, flow cytometry Clinical immunology Medium 33945871
2019 B7-H3 confers β-catenin-dependent co-localization; β-catenin co-localizes with B7-H3 and promotes its expression in adamantinomatous craniopharyngiomas, as shown by immunofluorescence and Western blot analysis. Immunofluorescence co-localization, Western blot analysis, immunohistochemistry on 44 craniopharyngioma samples Biochemical and biophysical research communications Low 31043272
2024 CAR T cells based on camel nanobodies recognizing the IgC domain (but not the IgV domain) of B7-H3 had more potent antitumor activity than IgV-targeting nanobody CAR-T cells. Single-cell RNA sequencing and T-cell proteomics identified top upregulated genes critical for polyfunctional CAR-T cell persistence, establishing the IgC epitope as optimal for CAR activation. Camel nanobody generation targeting IgC vs IgV epitopes, CAR-T cell construction, in vivo antitumor efficacy in mice, single-cell RNA sequencing, T-cell proteomics Nature communications Medium 37739951

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 CAR T Cells Targeting B7-H3, a Pan-Cancer Antigen, Demonstrate Potent Preclinical Activity Against Pediatric Solid Tumors and Brain Tumors. Clinical cancer research : an official journal of the American Association for Cancer Research 540 30655315
2016 Molecular Pathways: Targeting B7-H3 (CD276) for Human Cancer Immunotherapy. Clinical cancer research : an official journal of the American Association for Cancer Research 450 27208063
2017 Eradication of Tumors through Simultaneous Ablation of CD276/B7-H3-Positive Tumor Cells and Tumor Vasculature. Cancer cell 346 28399408
2020 B7-H3: An Attractive Target for Antibody-based Immunotherapy. Clinical cancer research : an official journal of the American Association for Cancer Research 330 33051306
2021 B7-H3/CD276: An Emerging Cancer Immunotherapy. Frontiers in immunology 248 34349762
2017 The third group of the B7-CD28 immune checkpoint family: HHLA2, TMIGD2, B7x, and B7-H3. Immunological reviews 203 28258693
2023 New frontiers in immune checkpoint B7-H3 (CD276) research and drug development. Molecular cancer 202 36859240
2019 B7-H3 promotes aerobic glycolysis and chemoresistance in colorectal cancer cells by regulating HK2. Cell death & disease 199 30952834
2020 B7-H3, a checkpoint molecule, as a target for cancer immunotherapy. International journal of biological sciences 193 32398947
2020 B7-H3 promotes colorectal cancer angiogenesis through activating the NF-κB pathway to induce VEGFA expression. Cell death & disease 176 31974361
2019 B7-H3 as a Novel CAR-T Therapeutic Target for Glioblastoma. Molecular therapy oncolytics 173 31485480
2022 Immune checkpoint of B7-H3 in cancer: from immunology to clinical immunotherapy. Journal of hematology & oncology 165 36284349
2018 B7-H3 Negatively Modulates CTL-Mediated Cancer Immunity. Clinical cancer research : an official journal of the American Association for Cancer Research 141 29530936
2021 B7-H3 Suppresses Antitumor Immunity via the CCL2-CCR2-M2 Macrophage Axis and Contributes to Ovarian Cancer Progression. Cancer immunology research 133 34799346
2021 The Role of CD276 in Cancers. Frontiers in oncology 110 33842369
2003 Mouse B7-H3 induces antitumor immunity. Gene therapy 109 12939639
2010 B7-h3 and its role in antitumor immunity. Clinical & developmental immunology 101 21127709
2023 mTORC1 upregulates B7-H3/CD276 to inhibit antitumor T cells and drive tumor immune evasion. Nature communications 96 36869048
2018 Genetic and clinical characterization of B7-H3 (CD276) expression and epigenetic regulation in diffuse brain glioma. Cancer science 85 30027617
2022 B7-H3 as a Therapeutic Target in Advanced Prostate Cancer. European urology 77 36114082
2017 B7-H3 promotes gastric cancer cell migration and invasion. Oncotarget 73 29069741
2023 Immune checkpoint B7-H3 is a therapeutic vulnerability in prostate cancer harboring PTEN and TP53 deficiencies. Science translational medicine 67 37163614
2012 A review of B7-H3 and B7-H4 immune molecules and their role in ovarian cancer. Gynecologic oncology 66 22910694
2023 Camel nanobody-based B7-H3 CAR-T cells show high efficacy against large solid tumours. Nature communications 65 37739951
2025 Histone lactylation-driven B7-H3 expression promotes tumor immune evasion. Theranostics 64 39990209
2022 Phase 1 study of intraventricular 131I-omburtamab targeting B7H3 (CD276)-expressing CNS malignancies. Journal of hematology & oncology 64 36371226
2024 B7-H3 Inhibitors in Oncology Clinical Trials: A Review. Journal of immunotherapy and precision oncology 60 38327753
2018 Tumor B7-H3 (CD276) Expression and Survival in Pancreatic Cancer. Journal of clinical medicine 60 29996538
2020 B7-H3 Immune Checkpoint Protein in Human Cancer. Current medicinal chemistry 58 31099317
2018 B7-H3 promotes metastasis, proliferation, and epithelial-mesenchymal transition in lung adenocarcinoma. OncoTargets and therapy 53 30127617
2021 The role of B7-H3 in tumors and its potential in clinical application. International immunopharmacology 51 34678689
2023 FDW028, a novel FUT8 inhibitor, impels lysosomal proteolysis of B7-H3 via chaperone-mediated autophagy pathway and exhibits potent efficacy against metastatic colorectal cancer. Cell death & disease 50 37537172
2018 B7-H3 in tumors: friend or foe for tumor immunity? Cancer chemotherapy and pharmacology 50 29299639
2023 Targeting DNA methylation and B7-H3 in RB1-deficient and neuroendocrine prostate cancer. Science translational medicine 47 37967200
2023 B7-H3 immunoregulatory roles in cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 46 37196544
2018 Negative roles of B7-H3 and B7-H4 in the microenvironment of cervical cancer. Experimental cell research 46 30099052
2017 Expression of CD24 and B7-H3 in breast cancer and the clinical significance. Oncology letters 46 29344150
2020 MiR-1253 exerts tumor-suppressive effects in medulloblastoma via inhibition of CDK6 and CD276 (B7-H3). Brain pathology (Zurich, Switzerland) 45 32145124
2020 B7-H3 regulates KIF15-activated ERK1/2 pathway and contributes to radioresistance in colorectal cancer. Cell death & disease 45 33011740
2011 B7-H3 and its relevance in cancer; immunological and non-immunological perspectives. Frontiers in bioscience (Elite edition) 38 21622107
2023 B7-H3 in Brain Malignancies: Immunology and Immunotherapy. International journal of biological sciences 37 37564196
2022 B7‑H3 promotes the epithelial‑mesenchymal transition of NSCLC by targeting SIRT1 through the PI3K/AKT pathway. Molecular medicine reports 37 35029291
2022 To kill a cancer: Targeting the immune inhibitory checkpoint molecule, B7-H3. Biochimica et biophysica acta. Reviews on cancer 36 36028149
2020 B7-H3 targeted antibody-based immunotherapy of malignant diseases. Expert opinion on biological therapy 36 33301369
2021 Targeting the immune checkpoint B7-H3 for next-generation cancer immunotherapy. Cancer immunology, immunotherapy : CII 35 34739560
2024 New Emerging Targets in Cancer Immunotherapy: The Role of B7-H3. Vaccines 33 38250867
2024 A Dual-Payload Antibody-Drug Conjugate Targeting CD276/B7-H3 Elicits Cytotoxicity and Immune Activation in Triple-Negative Breast Cancer. Cancer research 33 39186778
2023 B7-H3 specific CAR-T cells exhibit potent activity against prostate cancer. Cell death discovery 33 37149721
2023 EBV-Upregulated B7-H3 Inhibits NK cell-Mediated Antitumor Function and Contributes to Nasopharyngeal Carcinoma Progression. Cancer immunology research 32 36996321
2023 Antitumor activity of the investigational B7-H3 antibody-drug conjugate, vobramitamab duocarmazine, in preclinical models of neuroblastoma. Journal for immunotherapy of cancer 32 37775116
2024 High B7-H3 expression with low PD-L1 expression identifies armored-cold tumors in triple-negative breast cancer. NPJ breast cancer 31 38280882
2023 Exosomal B7-H3 facilitates colorectal cancer angiogenesis and metastasis through AKT1/mTOR/VEGFA pathway. Cellular signalling 31 37263461
2016 B7-H3 increases thymidylate synthase expression via the PI3k-Akt pathway. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 30 26787540
2024 Redirecting B7-H3.CAR T Cells to Chemokines Expressed in Osteosarcoma Enhances Homing and Antitumor Activity in Preclinical Models. Clinical cancer research : an official journal of the American Association for Cancer Research 28 39101835
2022 Pediatric medulloblastoma express immune checkpoint B7-H3. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 28 34988920
2019 The novel non-immunological role and underlying mechanisms of B7-H3 in tumorigenesis. Journal of cellular physiology 28 31222741
2023 B7-H3/CD276 and small-cell lung cancer: What's new? Translational oncology 27 37865049
2019 B7-H3 is regulated by BRD4 and promotes TLR4 expression in pancreatic ductal adenocarcinoma. The international journal of biochemistry & cell biology 27 30664982
2018 CD276 (B7-H3) Maintains Proliferation and Regulates Differentiation in Angiogenic Function in Late Endothelial Progenitor Cells. Stem cells (Dayton, Ohio) 27 30379377
2008 Circulating B7-H3(CD276) elevations in cerebrospinal fluid and plasma of children with bacterial meningitis. Journal of molecular neuroscience : MN 27 18690554
2021 B7-H3, Negatively Regulated by miR-128, Promotes Colorectal Cancer Cell Proliferation and Migration. Cell biochemistry and biophysics 26 33743142
2021 Fibronectin enhances tumor metastasis through B7-H3 in clear cell renal cell carcinoma. FEBS open bio 25 34431237
2016 Overexpression of B7-H3 correlates with aggressive clinicopathological characteristics in non-small cell lung cancer. Oncotarget 24 27835582
2022 Expression and clinical significance of VISTA, B7-H3, and PD-L1 in glioma. Clinical immunology (Orlando, Fla.) 23 36368642
2016 B7-H3 upregulates BRCC3 expression, antagonizing DNA damage caused by 5-Fu. Oncology reports 23 27175567
2022 The immune checkpoint B7-H3 (CD276) regulates adipocyte progenitor metabolism and obesity development. Science advances 22 35476450
2021 Expression, regulation and clinical significance of B7-H3 on neutrophils in human gastric cancer. Clinical immunology (Orlando, Fla.) 22 33945871
2020 High B7-H3 expression is linked to increased risk of prostate cancer progression. Pathology international 22 32776718
2024 Pan-Cancer Interrogation of B7-H3 (CD276) as an Actionable Therapeutic Target Across Human Malignancies. Cancer research communications 21 38709075
2023 B7-H3 in Pediatric Tumors: Far beyond Neuroblastoma. Cancers 21 37444389
2020 B7-H3 is spliced by SRSF3 in colorectal cancer. Cancer immunology, immunotherapy : CII 21 32719950
2024 CAR T cells redirected to B7-H3 for pediatric solid tumors: Current status and future perspectives. EJC paediatric oncology 19 38957786
2022 Hopes on immunotherapy targeting B7-H3 in neuroblastoma. Translational oncology 19 36327699
2019 Frequent B7-H3 overexpression in craniopharyngioma. Biochemical and biophysical research communications 19 31043272
2019 B7-H3 and its role in bone cancers. Pathology, research and practice 19 31060912
2019 Expression and Clinical Significance of Immune Checkpoint Regulator B7-H3 (CD276) in Human Meningioma. World neurosurgery 19 31629137
2022 Clinical significance and correlation of PD-L1, B7-H3, B7-H4, and TILs in pancreatic cancer. BMC cancer 18 35624419
2025 Tumor Immunotherapy Targeting B7-H3: From Mechanisms to Clinical Applications. ImmunoTargets and therapy 17 40171330
2023 Bispecific antibody targeting both B7-H3 and PD-L1 exhibits superior antitumor activities. Acta pharmacologica Sinica 17 37328649
2023 ITC-6102RO, a novel B7-H3 antibody-drug conjugate, exhibits potent therapeutic effects against B7-H3 expressing solid tumors. Cancer cell international 17 37596639
2021 B7-H3 inhibits apoptosis of gastric cancer cell by interacting with Fibronectin. Journal of Cancer 17 35003371
2019 B7-H3 modulates endothelial cell angiogenesis through the VEGF cytokine. Immunologic research 17 31292886
2011 Stimulation of B7-H3 (CD276) directs the differentiation of human marrow stromal cells to osteoblasts. Immunobiology 17 21893365
2024 B7-H3 Expression in Breast Cancer and Brain Metastasis. International journal of molecular sciences 16 38612786
2021 Advances in immunotherapeutic targets for childhood cancers: A focus on glypican-2 and B7-H3. Pharmacology & therapeutics 16 33992682
2021 Expression characteristic of 4Ig B7-H3 and 2Ig B7-H3 in acute myeloid leukemia. Bioengineered 16 34787059
2021 CD276 (B7H3) improve cancer stem cells formation in cervical carcinoma cell lines. Translational cancer research 16 35116240
2024 Non-immune functions of B7-H3: bridging tumor cells and the tumor vasculature. Frontiers in oncology 15 38952550
2023 B7-H3 confers stemness characteristics to gastric cancer cells by promoting glutathione metabolism through AKT/pAKT/Nrf2 pathway. Chinese medical journal 15 37488673
2022 B7-H3/CD276 Inhibitors: Is There Room for the Treatment of Metastatic Non-Small Cell Lung Cancer? International journal of molecular sciences 15 36555714
2021 B7-H3 regulates osteoclast differentiation via type I interferon-dependent IDO induction. Cell death & disease 15 34671026
2024 A promising target for breast cancer: B7-H3. BMC cancer 14 38326735
2022 TROP-2, Nectin-4, GPNMB, and B7-H3 Are Potentially Therapeutic Targets for Anaplastic Thyroid Carcinoma. Cancers 14 35158847
2021 Decreased m6A Modification of CD34/CD276(B7-H3) Leads to Immune Escape in Colon Cancer. Frontiers in cell and developmental biology 14 34307389
2020 Expression status of PD-L1 and B7-H3 in mesothelioma. Pathology international 14 33027549
2023 Influence of ADT on B7-H3 expression during CRPC progression from hormone-naïve prostate cancer. Cancer gene therapy 13 37452083
2021 Soluble B7-H3 in Ovarian Cancer and Its Predictive Value. Bulletin of experimental biology and medicine 13 34542756
2019 T cell cytotoxicity toward hematologic malignancy via B7-H3 targeting. Investigational new drugs 13 31267380
2024 B7-H3 is widely expressed in soft tissue sarcomas. BMC cancer 12 39478506
2025 Novel B7-H3 CAR T cells show potent antitumor effects in glioblastoma: a preclinical study. Journal for immunotherapy of cancer 11 39863300

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