Good Cop, Bad Cop
Cancer researcher Rita Fior uses zebrafish to study human cancer. Though this may seem like an unlikely match, her work shows great promise with forthcoming applications in personalised medicine.
The basic principle of Fior’s approach relies on transplanting human cancer cells into dozens of zebrafish larvae. The fish then serve as “living test tubes” where various treatments, such as different chemotherapy drugs, can be tested to reveal which works best. The assay is rapid, producing an answer within four short days.
Some years ago, when Fior was developing this assay, she noticed something curious. “The majority of human tumour cells successfully engrafted in the fish, but some tumours didn’t. They would just disappear within a day or two. However, when I treated the transplanted fish with chemotherapy, these tumors would not disappear anymore. They engrafted much more”, she recalls.
This seemingly paradoxical observation triggered a new working hypothesis. “Chemotherapy suppresses the immune system”, Fior explains. “If the tumour is rejected under normal conditions, but thrives in immuno-suppressed animals, then this points towards a new explanation: the fish’s immune system is actively destroying the cancer cells. Whereas in the ones that implant well, the tumour is able to suppress the fish’s immune system.”
Soon after, Fior, together with Vanda Povoa, a doctoral student in her lab at the Champalimaud Centre for the Unknown in Portugal, set off on a new research project. It’s main conclusions, published in the journal Nature Communications, advance our understanding of how cancer-immune interactions may lead to immunotherapy resistance and tumour growth. In the long run, these results may contribute to the development of new treatments and diagnostics.
Human tumor cells (in blue) being eliminated by macrophages (pink/yellow) in Zebrafish. Credit: Vanda Póvoa, Champalimaud Foundation.
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