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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.

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Fig. 1: Onco-foetal ecosystem in HCC.

References

  1. 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. 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).

    CAS  Article  Google Scholar 

  3. 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).

    CAS  Article  Google Scholar 

  4. 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).

    CAS  Article  Google Scholar 

  5. 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).

    CAS  Article  Google Scholar 

  6. 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. 7.

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

    CAS  Article  Google Scholar 

  8. 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. 9.

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

    CAS  Article  Google Scholar 

  10. 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).

    CAS  Article  Google Scholar 

  11. 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. 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. 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).

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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.

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

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Correspondence to Pierce Kah-Hoe Chow.

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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

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