A novel system to map protein interactions reveals evolutionarily conserved immune evasion pathways on transmissible cancers
| Autor: | Alana J. De Luca, A. Bruce Lyons, Peter R. Murphy, Amanda L. Patchett, Jocelyn M. Darby, Gregory M. Woods, Andrew S. Flies, Terry L. Pinfold, Chrissie E. B. Ong, Patrick R. Lennard |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_treatment
Evasion (network security) Biology Protein–protein interaction 03 medical and health sciences 0302 clinical medicine Immune system medicine Animals Research Articles Immune Evasion 030304 developmental biology Cancer Genetics 0303 health sciences Multidisciplinary SciAdv r-articles Immunotherapy Ligand (biochemistry) medicine.disease Fusion protein Immune checkpoint 3. Good health Marsupialia 030220 oncology & carcinogenesis Facial Neoplasms Research Article |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| Popis: | A simple cut-and-paste reagent development method applicable to any species reveals checkpoint molecules on transmissible cancers. Around 40% of humans and Tasmanian devils (Sarcophilus harrisii) develop cancer in their lifetime, compared to less than 10% for most species. In addition, devils are affected by two of the three known transmissible cancers in mammals. Immune checkpoint immunotherapy has transformed human medicine, but a lack of species-specific reagents has limited checkpoint immunology in most species. We developed a cut-and-paste reagent development system and used the fluorescent fusion protein system to show that immune checkpoint interactions are conserved across 160,000,000 years of evolution, CD200 is highly expressed on transmissible tumor cells, and coexpression of CD200R1 can block CD200 surface expression. The system’s versatility across species was demonstrated by fusing a fluorescent reporter to a camelid-derived nanobody that binds human programmed death ligand 1. The evolutionarily conserved pathways suggest that naturally occurring cancers in devils and other species can be used to advance our understanding of cancer and immunological tolerance. |
| Databáze: | OpenAIRE |
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