Embryonic development is characterized by rapidly dividing cells, cellular plasticity and a highly vascular microenvironment. These features are similar to those of tumour tissue, in that malignant cells are characterized by their ability to proliferate and exhibit cellular plasticity. The tumour microenvironment also often includes immunosuppressive features. Reciprocal communication between various cellular subpopulations enables fetal and tumour tissues to proliferate, migrate and escape immune responses. Fetal-like reprogramming has been demonstrated in the tumour microenvironment, indicating extraordinary cellular plasticity and bringing an additional layer of cellular heterogeneity. More importantly, some of these features are also present during inflammation. This Perspective discusses the similarity between embryogenesis, inflammation and tumorigenesis, and describes the mechanisms of oncofetal reprogramming that enable tumour cells to escape from immune responses, promoting tumour growth and metastasis.
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The authors thank D. Ackerman (Insight Editing London) for editing the manuscript during preparation. A.S. is supported by funding from the National Health and Medical Research Council (NHMRC) Ideas Grant (APP2010795), a Perkins–Curtin start-up fellowship and the Cancer Research Trust (CRT) Program Grant to the Liver Cancer Collaborative (LCC). J.C. is supported by a fellowship from the NHMRC Ideas Grant (APP2010795). F.G. is supported by the Singapore Agency for Science, Technology and Research (A*STAR) Biomedical Research Council Use-Inspired Basic Research (UIBR) Award, the Singapore National Research Foundation Senior Investigatorship (NRFI2017-02), the Fondation ARC “Leaders de demain” and the Fondation Gustave Roussy.
The authors declare no competing interests.
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Sharma, A., Blériot, C., Currenti, J. et al. Oncofetal reprogramming in tumour development and progression. Nat Rev Cancer 22, 593–602 (2022). https://doi.org/10.1038/s41568-022-00497-8