ArticleJournal for immunotherapy of cancer2020
SOX2 promotes resistance of melanoma with PD-L1 high expression to T-cell-mediated cytotoxicity that can be reversed by SAHA.
Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 50 citations in OpenAlex.
- Catestatin peptide impedes melanoma progression and drug resistance by reprogramming oncogenic signaling pathways.Oncogenesis · 2026Article
- Catestatin peptide impedes melanoma progression and drug resistance by reprogramming oncogenic signaling pathways.Research square · 2026Article
- Catestatin suppresses melanoma progression and drug resistance through multitargeted modulation of signaling pathways.bioRxiv : the preprint server for biology · 2025Article
- From intracellular drivers to immune modulators: emerging paradigms in oncogenic pathway-directed immunotherapy optimization.Cell communication and signaling : CCS · 2025Review
- A CD24BMC biology · 2025Article
- Lung Cancer-Intrinsic SOX2 Expression Mediates Resistance to Checkpoint Blockade Therapy by Inducing Treg-Dependent CD8+ T-cell Exclusion.Cancer immunology research · 2025Article
- Overexpressed Wnt-7a acts as a potential antitumor immune modulator and predicts poor prognosis in HNSCC.Heliyon · 2025Article
- PD-1 blockade treatment in melanoma: Mechanism of response and tumor-intrinsic resistance.Cancer science · 2025Review
- Role of the SOX family in cancer immune evasion: Emerging player and promising therapeutic opportunities.Medicine · 2025Review
- PD-1/PD-L1 inhibitor treatment associated with cardiotoxicity regulated by macrophage polarization and SOCS3/JAK/STAT3 signaling pathway.Central-European journal of immunology · 2025Article
- Network Medicine-Based Strategy Identifies Maprotiline as a Repurposable Drug by Inhibiting PD-L1 Expression via Targeting SPOP in Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Igniting Cold Tumors: Multi-Omics-Driven Strategies to Overcome Immune Evasion and Restore Immune Surveillance.Oncology research · 2025Review
- The combination of a PTP1B inhibitor, TNFR2 blocker, and PD‑1 antibody suppresses the progression of non‑small cell lung cancer tumors by enhancing immunocompetence.Oncology reports · 2024Article
- Cancer cell-specific PD-L1 expression is a predictor of poor outcome in patients with locally advanced oral cavity squamous cell carcinoma.Journal for immunotherapy of cancer · 2024Article
- Characterization of two melanoma cell lines resistant to BRAF/MEK inhibitors (vemurafenib and cobimetinib).Cell communication and signaling : CCS · 2024Article
- Review
- Article
- HDAC9 and miR-512 Regulate CAGE-Promoted Anti-Cancer Drug Resistance and Cellular Proliferation.Current issues in molecular biology · 2024Article
- The regulatory relationship between NAMPT and PD-L1 in cancer and identification of a dual-targeting inhibitor.EMBO molecular medicine · 2024Article
- Engineering a Programmed Death-Ligand 1-Targeting Monobody Via Directed Evolution for SynNotch-Gated Cell Therapy.ACS nano · 2024Article
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImmune checkpoint inhibitors (ICIs) induce better tumor regression in melanoma with programmed cell death 1 ligand 1 (PD-L1) high expression, but there has been an upsurge of failed responses. In this study, we aimed to explore the additional mechanisms possibly accounting for ICIs resistance and interventional strategies to overcome the resistance in melanoma with PD-L1 high expression.
methodsMelanoma xenografts and cytotoxicity assays were used to investigate function of SOX2 in regulating antitumor immunity. The activity of the janus kinase-signal transducer and activator of transcriptions (JAK-STAT) pathway was investigated by western blots, quantitative PCR and luciferase assay. Epigenetic compounds library screen was employed to identify inhibitors that could decrease SOX2 level. The effect of histone deacetylase inhibitor SAHA in antitumor immunity alone or in combination with immunotherapy was also determined in vitro and in vivo. Prognostic impact of SOX2 was analyzed using transcriptional profiles and clinical data download from the Gene Expression Omnibus and The Cancer Genome Atlas repository.
resultsWe uncovered a role of SOX2 in attenuating the sensitivity of melanoma cells to CD8+ T-cell killing. Mechanistically, SOX2 inhibited phosphatases suppressor of cytokine signaling 3 (SOCS3) and protein tyrosine phosphatase non-receptor type 1 (PTPN1) transcription, induced duration activation of the JAK-STAT pathway and thereby overexpression of interferon stimulated genes resistance signature (ISG.RS). By targeting the SOX2-JAK-STAT signaling, SAHA promoted the antitumor efficacy of IFNγ or anti-PD-1 in vitro and in vivo. Moreover, SOX2 was an independent prognostic factor for poor survival and resistant to anti-PD-1 therapy in melanoma with PD-L1 high expression.
conclusionsOur data unveiled an additional function of SOX2 causing immune evasion of CD8+ T-cell killing through alleviating the JAK-STAT pathway and ISG.RS expression. We also provided a rationale to explore a novel combination of ICIs with SAHA clinically, especially in melanoma with PD-L1 and SOX2 high expression.
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