Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Comment
  • Published:

A new perspective on the immune escape mechanism in HCC: onco-foetal reprogramming

Summary

We found a shared immunosuppressive microenvironment between foetal liver and hepatocellular carcinoma (HCC) which includes the re-emergence of foetal-associated endothelial cells (PLVAP/VEGFR2) and foetal-like (FOLR2) tumour-associated macrophages in HCC, mediated via VEGF–NOTCH signalling. The discoveries suggest possible novel targets for therapeutic interventions in HCC.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Onco-foetal ecosystem in HCC.

References

  1. Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A. & Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA. Cancer J. Clin. 68, 394–424 (2018).

    Article  Google Scholar 

  2. Zhai, W., Lim, T. K., Zhang, T., Phang, S. T., Tiang, Z., Guan, P. et al. The spatial organization of intra-tumour heterogeneity and evolutionary trajectories of metastases in hepatocellular carcinoma. Nat. Commun. 8, 4565 (2017).

    Article  CAS  Google Scholar 

  3. Kudo, M., Finn, R. S., Qin, S., Han, K.-H., Ikeda, K., Piscaglia, F. et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. The Lancet 391, 1163–1173 (2018).

    Article  CAS  Google Scholar 

  4. Finn, R. S., Qin, S., Ikeda, M., Galle, P. R., Ducreux, M., Kim, T. Y. et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N. Engl. J. Med. 382, 1894–1905 (2020).

    Article  CAS  Google Scholar 

  5. Sharma, A., Seow, J. J. W., Dutertre, C. A., Pai, R., Blériot, C., Mishra, A. et al. Onco-fetal reprogramming of endothelial cells drives immunosuppressive macrophages in hepatocellular carcinoma. Cell 183, 377–394.e321 (2020).

    Article  CAS  Google Scholar 

  6. Datta, M., Coussens, L. M., Nishikawa, H., Hodi, F. S. & Jain, R. K. Reprogramming the tumor microenvironment to improve immunotherapy: emerging strategies and combination therapies. Am. Soc. Clin. Oncol. Educ. Book https://doi.org/10.1200/edbk_237987, 165–174 (2019).

  7. Ohm, J. E. & Carbone, D. P. VEGF as a mediator of tumor-associated immunodeficiency. Immunol. Res. 23, 263–272 (2001).

    Article  CAS  Google Scholar 

  8. Pinter, M., Jain, R. K. & Duda, D. G. The current landscape of immune checkpoint blockade in hepatocellular carcinoma: a review. JAMA Oncol. 7, 113–123 (2021).

    Article  Google Scholar 

  9. Clevers, H. The cancer stem cell: premises, promises and challenges. Nat. Med. 17, 313–319 (2011).

    Article  CAS  Google Scholar 

  10. Prager, B. C., Xie, Q., Bao, S. & Rich, J. N. Cancer stem cells: the architects of the tumor ecosystem. Cell Stem Cell 24, 41–53 (2019).

    Article  CAS  Google Scholar 

  11. Wang, Y.-H., Cheng, T. Y., Chen, T. Y., Chang, K.M., Chuang, V. P. & Kao, K.-J. Plasmalemmal vesicle associated protein (PLVAP) as a therapeutic target for treatment of hepatocellular carcinoma. BMC Cancer 14, 815 (2014).

    Article  Google Scholar 

  12. Skytthe, M. K., Graversen, J. H. & Moestrup, S. K. Targeting of CD163(+) macrophages in inflammatory and malignant diseases. Int. J. Mol. Sci. 21, 5497 (2020).

  13. Yau, T. et al. Efficacy and safety of nivolumab plus ipilimumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib: The CheckMate 040 randomized clinical trial. JAMA Oncol. 6, e204564 (2020).

Download references

Acknowledgements

We would like to acknowledge the senior authors of the CELL article (DOI: 10.1016/j.cell.2020.08.040) for providing valuable insights to the commentary.

Author information

Authors and Affiliations

Authors

Contributions

S.C.C. and S.Y.C. discussed and prepared the commentary. P.K.C. discussed, reviewed and edited the commentary.

Corresponding author

Correspondence to Pierce Kah-Hoe Chow.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent to publish

Not applicable.

Data availability

Not applicable.

Competing interests

The authors declare no competing interests.

Funding information

Not applicable.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chew, S.C., Choo, S.Y. & Chow, P.KH. A new perspective on the immune escape mechanism in HCC: onco-foetal reprogramming. Br J Cancer 124, 1897–1899 (2021). https://doi.org/10.1038/s41416-021-01286-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41416-021-01286-0

This article is cited by

Search

Quick links