ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011
Association of IFN-gamma signal transduction defects with impaired HLA class I antigen processing in melanoma cell lines.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 71 citations in OpenAlex.
- Integrating interferon gamma receptor pathways, antigenicity, and immune contexture as predictors of immunotherapeutic strategies for mucosal melanomas.Journal for immunotherapy of cancer · 2026Article
- HIV status alters immune cell infiltration and activation profile in women with breast cancer.Nature communications · 2025Article
- Altered ACE2 and interferon landscape in the COVID-19 microenvironment correlate with the anti-PD-1 response in solid tumors.Cellular and molecular life sciences : CMLS · 2024Article
- Correlation of the tumor escape phenotype with loss of PRELP expression in melanoma.Journal of translational medicine · 2023Article
- Regional Variation in the Tumor Microenvironment, Immune Escape and Prognostic Factors in Breast Cancer in Sub-Saharan Africa.Cancer immunology research · 2023Article
- Interferons and Resistance Mechanisms in Tumors and Pathogen-Driven Diseases-Focus on the Major Histocompatibility Complex (MHC) Antigen Processing Pathway.International journal of molecular sciences · 2023Review
- Selective multi-kinase inhibition sensitizes mesenchymal pancreatic cancer to immune checkpoint blockade by remodeling the tumor microenvironment.Nature cancer · 2022Article
- MHC heterogeneity and response of metastases to immunotherapy.Cancer metastasis reviews · 2021Review
- Investigating T Cell Immunity in Cancer: Achievements and Prospects.International journal of molecular sciences · 2021Review
- HLA class I loss in colorectal cancer: implications for immune escape and immunotherapy.Cellular & molecular immunology · 2021Review
- The MHC Class-I Transactivator NLRC5: Implications to Cancer Immunology and Potential Applications to Cancer Immunotherapy.International journal of molecular sciences · 2021Review
- Tumor Microenvironment, HLA Class I and APM Expression in HPV-Negative Oral Squamous Cell Carcinoma.Cancers · 2021Article
- Immune Therapy Resistance and Immune Escape of Tumors.Cancers · 2021Review
- Targeting the innate immunoreceptor RIG-I overcomes melanoma-intrinsic resistance to T cell immunotherapy.The Journal of clinical investigation · 2020Article
- Distinctive germline expression of class I human leukocyte antigen (HLA) alleles and DRB1 heterozygosis predict the outcome of patients with non-small cell lung cancer receiving PD-1/PD-L1 immune checkpoint blockade.Journal for immunotherapy of cancer · 2020Article
- Efficient Induction of Cytotoxic T Cells by Viral Vector Vaccination Requires STING-Dependent DC Functions.Frontiers in immunology · 2020Article
- Tumor-induced escape mechanisms and their association with resistance to checkpoint inhibitor therapy.Cancer immunology, immunotherapy : CII · 2019Review
- Cell-state dynamics and therapeutic resistance in melanoma from the perspective of MITF and IFNγ pathways.Nature reviews. Clinical oncology · 2019Review
- Interferon signaling in cancer. Non-canonical pathways and control of intracellular immune checkpoints.Seminars in immunology · 2019Review
- Cancer Neoepitopes for Immunotherapy: Discordance Between Tumor-Infiltrating T Cell Reactivity and Tumor MHC Peptidome Display.Frontiers in immunology · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeAbnormalities in the constitutive and IFN-γ-inducible HLA class I surface antigen expression of tumor cells is often associated with an impaired expression of components of the antigen processing machinery (APM). Hence, we analyzed whether there exists a link between the IFN-γ signaling pathway, constitutive HLA class I APM component expression, and IFN-γ resistance. EXPERIMENTAL
designThe basal and IFN-γ-inducible expression profiles of HLA class I APM and IFN-γ signal transduction cascade components were assessed in melanoma cells by real-time PCR (RT-PCR), Western blot analysis and/or flow cytometry, the integrity of the Janus activated kinase (JAK) 2 locus by comparative genomic hybridization. JAK2 was transiently overexpressed in JAK2(-) cells. The effect of IFN-γ on the cell growth was assessed by XTT [2,3-bis(2-methoxy-4-nitro-S-sulfophenynl)-H-tetrazolium-5-carboxanilide inner salt] assay.
resultsThe analysis of 8 melanoma cell lines linked the IFN-γ unresponsiveness of Colo 857 cells determined by lack of inducibility of HLA class I surface expression on IFN-γ treatment to a deletion of JAK2 on chromosome 9, whereas other IFN-γ signaling pathway components were not affected. In addition, the constitutive HLA class I APM component expression levels were significantly reduced in JAK2(-) cells. Furthermore, JAK2-deficient cells were also resistant to the antiproliferative effect of IFN-γ. Transfection of wild-type JAK2 into JAK2(-) Colo 857 not only increased the basal APM expression but also restored their IFN-γ sensitivity.
conclusionsImpaired JAK2 expression in melanoma cells leads to reduced basal expression of MHC class I APM components and impairs their IFN-γ inducibility, suggesting that malfunctional IFN-γ signaling might cause HLA class I abnormalities.
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Registered trials
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.