ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
SHP2 is overexpressed and inhibits pSTAT1-mediated APM component expression, T-cell attracting chemokine secretion, and CTL recognition in head and neck cancer cells.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 75 citations in OpenAlex.
- Afatinib and Pembrolizumab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (ALPHA Study): A Phase II Study with Biomarker Analysis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- EGFR activation disrupts immunotherapy response via SHP2-mediated suppression of tumor-intrinsic response to IFN-γ.The Journal of clinical investigation · 2026Article
- Antigen processing machinery deficits in head and neck cancers: mechanisms of immune evasion and strategies for therapeutic restoration.Frontiers in oncology · 2026Review
- The regulatory role and mechanism of energy metabolism and immune response in head and neck cancer.Genes & diseases · 2025Review
- Orlistat facilitates immunotherapy via AKT-FOXO3a-FOXM1-mediated PD-L1 suppression.Journal for immunotherapy of cancer · 2025Article
- SHP2 as a primordial epigenetic enzyme expunges histone H3 pTyr-54 to amend androgen receptor homeostasis.Nature communications · 2024Article
- Immune escape of head and neck cancer mediated by the impaired MHC-I antigen presentation pathway.Oncogene · 2024Review
- Rescue of NLRC5 expression restores antigen processing machinery in head and neck cancer cells lacking functional STAT1 and p53.Cancer immunology, immunotherapy : CII · 2024Article
- Review
- Review
- Mometasone Furoate Inhibits the Progression of Head and Neck Squamous Cell Carcinoma via Regulating Protein Tyrosine Phosphatase Non-Receptor Type 11.Biomedicines · 2023Article
- Major histocompatibility complex class I molecule expression by pancreatic cancer cells is regulated by activation and inhibition of the epidermal growth factor receptor.Immunologic research · 2022Article
- Immune-Related Mutational Landscape and Gene Signatures: Prognostic Value and Therapeutic Impact for Head and Neck Cancer.Cancers · 2021Review
- Review
- Targeting MHC Regulation Using Polycyclic Polyprenylated Acylphloroglucinols Isolated fromBiomolecules · 2020Article
- MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy.Cancers · 2020Review
- Phosphoinositide 3-Kinase Signaling Can Modulate MHC Class I and II Expression.Molecular cancer research : MCR · 2019Article
- Tumour Microenvironment and Immune Evasion in EGFR Addicted NSCLC: Hurdles and Possibilities.Cancers · 2019Review
- How patients with an intact immune system develop head and neck cancer.Oral oncology · 2019Review
- Role of Tumor-Associated Macrophages in the Clinical Course of Pancreatic Neuroendocrine Tumors (PanNETs).Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
purposeHuman leukocyte antigen (HLA) class I antigen processing machinery (APM) component downregulation permits escape of malignant cells from recognition by cytotoxic T lymphocytes (CTL) and correlates with poor prognosis in patients with head and neck cancer (HNC). Activated STAT1 (pSTAT1) is necessary for APM component expression in HNC cells. We investigated whether an overexpressed phosphatase was responsible for basal suppression of pSTAT1 and subsequent APM component-mediated immune escape in HNC cells. EXPERIMENTAL
designImmunohistochemical staining and reverse transcription PCR of paired HNC tumors was performed for the phosphatases src homology domain-containing phosphatase (SHP)-1 and SHP2. Depletion of phosphatase activity in HNC and STAT1(-/-) tumor cells was achieved by siRNA knockdown. HLA class I-restricted, tumor antigen-specific CTL were used in IFN-γ ELISPOT assays against HNC cells. Chemokine secretion was measured after SHP2 depletion in HNC cells.
resultsSHP2, but not SHP1, was significantly upregulated in HNC tissues. In HNC cells, SHP2 depletion significantly upregulated expression of pSTAT1 and HLA class I APM components. Overexpression of SHP2 in nonmalignant keratinocytes inhibited IFN-γ-mediated STAT1 phosphorylation, and SHP2 depletion in STAT1(-/-) tumor cells did not significantly induce IFN-γ-mediated APM component expression, verifying STAT1 dependence of SHP2 activity. SHP2 depletion induced recognition of HNC cells by HLA class I-restricted CTL and secretion of inflammatory, T-cell attracting chemokines, RANTES and IP10.
conclusionThese findings suggest for the first time an important role for SHP2 in APM-mediated escape of HNC cells from CTL recognition. Targeting SHP2 could enhance T-cell-based cancer immunotherapy.
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