ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
USP22 deficiency in melanoma mediates resistance to T cells through IFNγ-JAK1-STAT1 signal axis.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 24 citations in OpenAlex.
- A ZDHHC3-USP5-PTRF axis links palmitoylation to ferroptosis-associated phenotypes in melanoma.Cell death & disease · 2026Article
- USP9X regulates copper-induced CASP9/CASP3/GSDME-dependent pyroptosis by deubiquitinating JAK1.Apoptosis : an international journal on programmed cell death · 2026Article
- Lytic IFNγ is stored in cytotoxic granules and coreleased with granzyme B to mediate cytotoxic T lymphocyte killing.Cellular & molecular immunology · 2026Article
- Scissor-CIBERSORTx Deconvolution Reveals Functional Heterogeneity of CTAL/aTAL Cells and Associated Biomarkers in Renal Fibrosis.Current issues in molecular biology · 2026Article
- CUL5 E3 ubiquitin ligase regulates the evasion of bladder cancer cells to CD8+ T cell-mediated killing by inhibiting autophagy.PLoS biology · 2026Article
- High-throughput screening to engineer optimal T cell therapies: current knowledge and future prospects.Frontiers in oncology · 2026Review
- Therapy-induced senescent glioblastoma cells sustain a procancer immune microenvironment by activating DDX58-mediated STAT1 signaling.Neuro-oncology · 2025Article
- Keratin 6A promotes skin inflammation through JAK1-STAT3 activation in keratinocytes.Journal of biomedical science · 2025Article
- GDP-bound Rab37 modulates M2-like tumor-associated macrophage polarization by attenuating STAT1 translocation to downregulate the type I IFN pathway.British journal of cancer · 2025Article
- Formin protein DAAM1 positively regulates PD-L1 expression via mediating the JAK1/STAT1 axis in pancreatic cancer.Cancer cell international · 2025Article
- IFN-gamma in the tumor microenvironment: dual roles in cancer progression and therapy.EXCLI journal · 2025Review
- High-throughput screening for optimizing adoptive T cell therapies.Experimental hematology & oncology · 2024Review
- Demethylzeylasteral induces PD-L1 ubiquitin-proteasome degradation and promotes antitumor immunityActa pharmaceutica Sinica. B · 2024Article
- Ubiquitin modification in the regulation of tumor immunotherapy resistance mechanisms and potential therapeutic targets.Experimental hematology & oncology · 2024Review
- Article
- Drug resistance mechanisms and treatment strategies mediated by Ubiquitin-Specific Proteases (USPs) in cancers: new directions and therapeutic options.Molecular cancer · 2024Review
- Advances in Ferroptosis-Inducing Agents by Targeted Delivery System in Cancer Therapy.International journal of nanomedicine · 2024Review
- Tumor-intrinsicOncoimmunology · 2023Article
- Unveiling immune checkpoint regulation: exploring the power ofFrontiers in genetics · 2023Review
- Application of CRISPR screen in mechanistic studies of tumor development, tumor drug resistance, and tumor immunotherapy.Frontiers in cell and developmental biology · 2023Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated 9 (Cas9)-mediated loss-of-function screens are powerful tools for identifying genes responsible for diverse phenotypes. Here, we perturbed genes in melanoma cells to screen for genes involved in tumor escape from T cell-mediated killing. Multiple interferon gamma (IFNγ) signaling-related genes were enriched in melanoma cells resistant to T cell killing. In addition, deletion of the deubiquitinating protease ubiquitin specific peptidase 22 (USP22) in mouse melanoma (B16-OVA) cells decreased the efficacy of T cell-mediated killing, both in vitro and in vivo, while overexpression enhanced tumor-cell sensitivity to T (OT-I) cell-mediated killing. USP22 deficiency in both mouse and human melanoma cells showed impaired sensitivity to interferon pathway and USP22 was positively correlated with key molecules of interferon pathway in clinical melanoma samples. Mechanistically, USP22 may directly interact with signal transducer and activator of transcription 1 (STAT1), deubiquitinate it, and improve its stability in both human and mouse melanoma cells. Our findings identified a previously unknown function of USP22 and linked the loss of genes in tumor cells that are essential for escaping the effector function of CD8
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