ArticleJournal for immunotherapy of cancer2022
Genome-scale CRISPR-Cas9 screen reveals novel regulators of B7-H3 in tumor cells.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Emerging CRISPR Approaches for Countering Immune Evasion: Insight from Recent Studies.International journal of molecular sciences · 2026Review
- Exploiting B7-H3: Molecular Insights and Immunotherapeutic Strategies for Osteosarcoma.Bioengineering (Basel, Switzerland) · 2025Review
- A novel immunocytokine promotes T cell- and cytokine-induced killer cell-mediated antitumor immunity via a non-MHC-restricted mechanism in glioblastoma.Journal of translational medicine · 2025Article
- Bibliometric analysis of global research hotspots in ovarian cancer immunotherapy from 2014 to 2024 using CiteSpace.Human vaccines & immunotherapeutics · 2025Article
- B7-H3 in the tumor microenvironment: Implications for CAR T cell therapy in pediatric solid tumors.Cancer metastasis reviews · 2025Review
- Revealing genetic drivers of ovarian cancer and chemoresistance: insights from whole-genome CRISPR-knockout library screens.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Paeoniflorin Inhibits Porcine Circovirus Type 2 Replication by Inhibiting Autophagy and Targeting AKT/mTOR Signaling.Veterinary sciences · 2025Article
- Research progress of B7-H3 in malignant tumors.Frontiers in immunology · 2025Review
- The relevance of B7-H3 and tumor-associated macrophages in the tumor immune microenvironment of solid tumors: recent advances.American journal of translational research · 2025Review
- Retinol binding protein 4 restricts PCV2 replication via selective autophagy degradation of viral ORF1 protein.Communications biology · 2024Article
- Tangshen formula improves diabetic nephropathy in STZ-induced diabetes rats fed with hyper-methionine by regulating the methylation status of kidney.Clinical epigenetics · 2024Article
- New frontiers in immune checkpoint B7-H3 (CD276) research and drug development.Molecular cancer · 2023Review
- Evaluation of B7-H3 Targeted Immunotherapy in a 3D Organoid Model of Craniopharyngioma.Biomolecules · 2022Article
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDespite advances in B7 homolog 3 protein (B7-H3) based immunotherapy, the development of drug resistance remains a major clinical concern. The heterogeneity and emerging loss of B7-H3 expression are the main causes of drug resistance and treatment failure in targeted therapies, which reveals an urgent need to elucidate the mechanism underlying the regulation of B7-H3 expression. In this study, we identified and explored the crucial role of the transcription factor SPT20 homolog (SP20H) in B7-H3 expression and tumor progression.
methodsHere, we performed CRISPR/Cas9-based genome scale loss-of-function screening to identify regulators of B7-H3 in human ovarian cancer cells. Signaling pathways altered by SP20H knockout were revealed by RNA sequencing. The regulatory role and mechanism of SP20H in B7-H3 expression were validated using loss-of-function and gain-of-function assays in vitro. The effects of inhibiting SP20H on tumor growth and efficacy of anti-B7-H3 treatment were evaluated in tumor-bearing mice.
resultsWe identified SUPT20H (SP20H) as negative and eIF4E as positive regulators of B7-H3 expression in various cancer cells. Furthermore, we provided evidence that either SP20H loss or TNF-α stimulation in tumor cells constitutively activates p38 MAPK-eIF4E signaling, thereby upregulating B7-H3 expression. Loss of SP20H upregulated B7-H3 expression both in vitro and in vivo. Additionally, deletion of SP20H significantly suppressed tumor growth and increased immune cells infiltration in tumor microenvironment. More importantly, antibody-drug conjugates targeting B7-H3 exhibited superior antitumor performance against SP20H-deficient tumors relative to control groups.
conclusionsActivation of p38 MAPK-eIF4E signaling serves as a key event in the transcription initiation and B7-H3 protein expression in tumor cells. Genetically targeting SP20H upregulates target antigen expression and sensitizes tumors to anti-B7-H3 treatment. Collectively, our findings provide new insight into the mechanisms underlying B7-H3 expression and introduce a potential synergistic target for existing antibody-based targeted therapy against B7-H3.
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