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  • Perspective
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Oncofetal reprogramming in tumour development and progression

Nature Reviews Cancer volume 22, pages 593–602 (2022)Cite this article

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Abstract

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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Fig. 1: Similarities between embryogenesis, inflammation and tumorigenesis.
Fig. 2: Timeline of developments in the history of oncofetal reprogramming.
Fig. 3: Mechanism of oncofetal reprogramming.
Fig. 4: Oncofetal score as a predictor of treatment response.

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Acknowledgements

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.

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Authors and Affiliations

  1. Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, Western Australia, Australia

    Ankur Sharma & Jennifer Currenti

  2. Curtin Medical School, Curtin University, Bentley, Western Australia, Australia

    Ankur Sharma & Jennifer Currenti

  3. Curtin Health Innovation Research Institute, Curtin University, Bentley, Western Australia, Australia

    Ankur Sharma

  4. Institute of Molecular and Cellular Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore

    Ankur Sharma

  5. INSERM U1015, Institut Gustave Roussy, Villejuif, France

    Camille Blériot & Florent Ginhoux

  6. Singapore Immunology Network, Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore

    Florent Ginhoux

  7. Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Florent Ginhoux

  8. Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore

    Florent Ginhoux

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  1. Ankur Sharma
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A.S. and F.G. conceptualized the Perspective. A.S., C.B. and F.G. contributed equally to all other aspects of the article. J.C. contributed substantially to discussion of the content, writing the article and review of the manuscript before submission.

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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

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