ArticleJournal of cancer research and clinical oncology2021
NLRC5 regulates expression of MHC-I and provides a target for anti-tumor immunity in transmissible cancers.
Article in Journal of cancer research and clinical oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 23 citations in OpenAlex.
- Identification of expressed endogenous retroviral element associated long terminal repeats in devil facial tumour cells.Open biology · 2026Article
- Copolymers of NVAm and NVP for Efficient Gene Delivery.ACS polymers Au · 2026Article
- RFX5 in cancer: context-dependent molecular functions and emerging translational relevance.Frontiers in immunology · 2026Review
- Unlocking the genetic code: a comprehensive Genome-Wide association study and gene set enrichment analysis of cell-mediated immunity in chickens.BMC genomics · 2025Article
- Differentially expressed growth factors and cytokines drive phenotypic changes in transmissible cancers.Discovery immunology · 2025Article
- Conversion of Mouse-Derived Hybridomas to Tasmanian Devil Recombinant IgG Antibodies.Methods in molecular biology (Clifton, N.J.) · 2024Article
- NLRC5 overexpression in ovarian tumors remodels the tumor microenvironment and increases T-cell reactivity toward autologous tumor-associated antigens.Frontiers in immunology · 2023Article
- Class II transactivator induces expression of MHC-I and MHC-II in transmissible Tasmanian devil facial tumours.Open biology · 2022Article
- Article
- Expression of the Nonclassical MHC Class I, Saha-UD in the Transmissible Cancer Devil Facial Tumour Disease (DFTD).Pathogens (Basel, Switzerland) · 2022Article
- Comparative Transcriptome Analysis of Spleen Reveals Potential Regulation of Genes and Immune Pathways Following Administration of Aeromonas salmonicida subsp. masoucida Vaccine in Atlantic Salmon (Salmo salar).Marine biotechnology (New York, N.Y.) · 2022Article
- Applied ecoimmunology: using immunological tools to improve conservation efforts in a changing world.Conservation physiology · 2021Article
- Transcriptomic Profiling of Fibropapillomatosis in Green Sea Turtles (Frontiers in immunology · 2021Article
- Biomimetics provides lessons from nature for contemporary ways to improve human health.Journal of clinical and translational science · 2021Review
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
purposeDownregulation of MHC class I (MHC-I) is a common immune evasion strategy of many cancers. Similarly, two allogeneic clonal transmissible cancers have killed thousands of wild Tasmanian devils (Sarcophilus harrisii) and also modulate MHC-I expression to evade anti-cancer and allograft responses. IFNG treatment restores MHC-I expression on devil facial tumor (DFT) cells but is insufficient to control tumor growth. Transcriptional co-activator NLRC5 is a master regulator of MHC-I in humans and mice but its role in transmissible cancers remains unknown. In this study, we explored the regulation and role of MHC-I in these unique genetically mis-matched tumors.
methodsWe used transcriptome and flow cytometric analyses to determine how MHC-I shapes allogeneic and anti-tumor responses. Cell lines that overexpress NLRC5 to drive antigen presentation, and B2M-knockout cell lines incapable of presenting antigen on MHC-I were used to probe the role of MHC-I in rare cases of tumor regressions.
resultsTranscriptomic results suggest that NLRC5 plays a major role in MHC-I regulation in devils. NLRC5 was shown to drive the expression of many components of the antigen presentation pathway but did not upregulate PDL1. Serum from devils with tumor regressions showed strong binding to IFNG-treated and NLRC5 cell lines; antibody binding to IFNG-treated and NRLC5 transgenic tumor cells was diminished or absent following B2M knockout.
conclusionMHC-I could be identified as a target for anti-tumor and allogeneic immunity. Consequently, NLRC5 could be a promising target for immunotherapy and vaccines to protect devils from transmissible cancers and inform development of transplant and cancer therapies for humans.
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