ArticleBritish journal of cancer2007
Multiple mechanisms underlie defective recognition of melanoma cells cultured in three-dimensional architectures by antigen-specific cytotoxic T lymphocytes.
Article in British journal of cancer, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 98 citations in OpenAlex.
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- Preclinical models for development of immune-oncology therapies.Immuno-oncology insights · 2022Article
- Role of Hypoxia in the Interferon Response.Frontiers in immunology · 2022Review
- Going with the Flow: Modeling the Tumor Microenvironment Using Microfluidic Technology.Cancers · 2021Review
- Engineered in vitro tumor models for cell-based immunotherapy.Acta biomaterialia · 2021Review
- Review
- Hypoxia and Extracellular Acidification as Drivers of Melanoma Progression and Drug Resistance.Cells · 2021Review
- Engineering approaches for studying immune-tumor cell interactions and immunotherapy.iScience · 2021Review
- Hypoxia Regulates Endogenous Double-Stranded RNA ProductionFrontiers in oncology · 2021Article
- Innate Lymphoid Cells in Skin Homeostasis and Malignancy.Frontiers in immunology · 2021Review
- CAIX Regulates GBM Motility and TAM Adhesion and Polarization through EGFR/STAT3 under Hypoxic Conditions.International journal of molecular sciences · 2020Article
- Blockade of Lactate Dehydrogenase-A (LDH-A) Improves Efficacy of Anti-Programmed Cell Death-1 (PD-1) Therapy in Melanoma.Cancers · 2019Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer cells' growth in three-dimensional (3D) architectures promotes resistance to drugs, cytokines, or irradiation. We investigated effects of 3D culture as compared to monolayers (2D) on melanoma cells' recognition by tumour-associated antigen (TAA)-specific HLA-A(*)0201-restricted cytotoxic T-lymphocytes (CTL). Culture of HBL, D10 (both HLA-A(*)0201+, TAA+) and NA8 (HLA-A(*)0201+, TAA-) melanoma cells on polyHEMA-coated plates, resulted in generation of 3D multicellular tumour spheroids (MCTS). Interferon-gamma (IFN-gamma) production by HLA-A(*)0201-restricted Melan-A/MART-1(27-35) or gp 100(280-288)-specific CTL clones served as immunorecognition marker. Co-culture with melanoma MCTS, resulted in defective TAA recognition by CTL as compared to 2D as witnessed by decreased IFN-gamma production and decreased Fas Ligand, perforin and granzyme B gene expression. A multiplicity of mechanisms were potentially involved. First, MCTS per se limit CTL capacity of recognising HLA class I restricted antigens by reducing exposed cell surfaces. Second, expression of melanoma differentiation antigens is downregulated in MCTS. Third, expression of HLA class I molecules can be downregulated in melanoma MCTS, possibly due to decreased interferon-regulating factor-1 gene expression. Fourth, lactic acid production is increased in MCTS, as compared to 2D. These data suggest that melanoma cells growing in 3D, even in the absence of immune selection, feature characteristics capable of dramatically inhibiting TAA recognition by specific CTL.
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