ArticleJournal for immunotherapy of cancer2022
SP140 inhibits STAT1 signaling, induces IFN-γ in tumor-associated macrophages, and is a predictive biomarker of immunotherapy response.
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 20 papers, 2 of them syntheses that pooled it.
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Who cites it
20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 33 citations in OpenAlex.
- Clinical and mechanistic insights into the expression of SP100 family proteins in various cancers: a systematic review.BMC cancer · 2025Pooled it
- Inflammatory markers as prognostic markers in patients with head and neck squamous cell carcinoma treated with immune checkpoint inhibitors: a systematic review and meta-analysis.Frontiers in oncology · 2024Pooled it
- Dynamics of tumor ecosystems and microbiome in response to neoadjuvant ABFOLFOX treatment in patients with unresectable colorectal cancer with liver metastasis.Genome medicine · 2026Trial
- CXCL10 as a migration-associated biomarker in oral squamous cell carcinoma.BMC oral health · 2026Article
- The cost of persistent alarm: temporal transcriptional reprogramming of macrophages from acute activation to chronic immune suppression by day 11.Frontiers in immunology · 2026Article
- Tumor-associated macrophages in cancer: from mechanisms to application.Molecular biomedicine · 2025Review
- Article
- Protein Kinase C δ: a critical hub regulating macrophage immunomodulatory functions duringbioRxiv : the preprint server for biology · 2025Article
- A 3D Self-Assembly Platform Integrating Decellularized Matrix Recapitulates In Vivo Tumor Phenotypes and Heterogeneity.Cancer research · 2025Article
- PTEN as a prognostic factor for radiotherapy plus immunotherapy response in nasopharyngeal carcinoma.Journal of nanobiotechnology · 2025Article
- Multi-omics in immunotherapy research for HNSCC: present situation and future perspectives.NPJ precision oncology · 2025Review
- The SP140-RESIST pathway regulates interferon mRNA stability and antiviral immunity.bioRxiv : the preprint server for biology · 2025Article
- Molecular insights into immune evasion in head and neck squamous cell carcinomas: Toward a promising treatment strategy.Oncology research · 2025Review
- Machine learning-based identification of histone deacetylase-associated prognostic factors and prognostic modeling for low-grade glioma.Discover oncology · 2024Article
- An endogenous retrovirus regulates tumor-specific expression of the immune transcriptional regulator SP140.Human molecular genetics · 2024Article
- Review
- PI3Kγ inhibition combined with DNA vaccination unleashes a B-cell-dependent antitumor immunity that hampers pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Engineering Tumor Stroma Morphogenesis Using Dynamic Cell-Matrix Spheroid Assembly.bioRxiv : the preprint server for biology · 2024Article
- SP140 inhibitor suppressing TRIM22 expression regulates glioma progress through PI3K/AKT signaling pathway.Brain and behavior · 2024Article
- A deep learning approach based on multi-omics data integration to construct a risk stratification prediction model for skin cutaneous melanoma.Journal of cancer research and clinical oncology · 2023Article
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Authors and funding
12 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundUnderstanding the role and potential therapeutic targeting of tumor-associated macrophages (TAMs) is crucial to developing new biomarkers and therapeutic strategies for cancer immunotherapies. The epigenetic reader SP140 has emerged as a master regulator of macrophage transcriptional programs; however, its role in the signaling of TAMs and response to immunotherapy has not been investigated.
methodsWe evaluated the correlation between SP140 expression in head and neck squamous cell carcinoma (HNSCC) TAMs and clinical outcomes. We also used complementary bioinformatics and experimental approaches to study the association of SP140 expression with tumor mutation burden, patient survival, immunogenic signature of tumors, and signaling of TAMs. SP140 overexpression or knockdown was implemented to identify the role of SP140 in downstream signaling and production of inflammatory cytokine and chemokines. Chromatin immunoprecipitation and analysis of assay of transposase accessible chromatin sequencing data were used to demonstrate the direct binding of SP140 on the promoters of STAT1. Finally, correlation of SP140 with immune cell infiltrates and response to immune-checkpoint blockade in independent cohorts of HNSCC, metastatic melanoma, and melanoma was assessed.
resultsWe found that SP140 is highly expressed in TAMs across many cancer types, including HNSCCs. Interestingly, higher expression of SP140 in the tumors was associated with higher tumor mutation burden, improved survival, and a favorable response to immunotherapy. Tumors with high SP140 expression showed enrichment of inflammatory response and interferon-gamma (IFN-γ) pathways in both pan-cancer analysis and HNSCC-specific analysis. Mechanistically, SP140 negatively regulates transcription and phosphorylation of STAT1 and induces IFN-γ signaling. Activating SP140 in macrophages and TAMs induced the proinflammatory macrophage phenotype, increased the antitumor activity of macrophages, and increased the production of IFN-γ and antitumor cytokines and chemokines including interleukin-12 and CXCL10. SP140 expression provided higher sensitivity and specificity to predict antiprogrammed cell death protein 1 immunotherapy response compared with programmed death-ligand 1 in HNSCCs and lung cancer. In metastatic melanoma, higher levels of SP140 were associated with a durable response to immunotherapy, higher immune score estimates, high infiltrations of CD8
conclusionsOur findings suggest that SP140 could serve as both a therapeutic target and a biomarker to identify immunotherapy responders.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.