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TUMOR IMMUNOLOGY

PARP11 interfer(on)es with CAR T cell efficacy

Despite the remarkable success of chimeric antigen receptor (CAR) T cell therapies in the treatment of hematological malignancies, this strategy remains challenging in solid tumors. One major obstacle is the hostile immunosuppressive tumor microenvironment. New research demonstrates that targeting PARP11 can overcome this immunosuppression and boost CAR T cell efficacy through stabilization of IFNAR1.

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Fig. 1: T cell immunosuppression induced by the adenosine–PARP11–IFNAR1 pathway.

References

  1. Mardiana, S. et al. Sci. Transl Med. 11, eaaw2293 (2019).

    Article  CAS  Google Scholar 

  2. Rafiq, S., Hackett, C. S. & Brentjens, R. J. Nat. Rev. Clin. Oncol. 17, 147–167 (2020).

    Article  Google Scholar 

  3. Rupp, L. J. et al. Sci. Rep. 7, 737 (2017).

    Article  Google Scholar 

  4. Parker, B. S., Rautela, J. & Hertzog, P. J. Nat. Rev. Cancer 16, 131–144 (2016).

    Article  Google Scholar 

  5. Katlinski, K. V. et al. Cancer Cell 31, 194–207 (2017).

    Article  CAS  Google Scholar 

  6. Zhang, H. et al. Nat. Cancer https://doi.org/10.1038/s43018-022-00383-0 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Guo, T. et al. Nat. Microbiol. 4, 1872–1884 (2019).

    Article  CAS  Google Scholar 

  8. Bhattacharya, S. et al. J. Biol. Chem. 286, 22069–22076 (2011).

    Article  CAS  Google Scholar 

  9. Spiegelman, V. S. et al. Mol. Cell 5, 877–882 (2000).

    Article  CAS  Google Scholar 

  10. Stadtmauer, E. A. et al. Science 367, eaba7365 (2020).

    Article  CAS  Google Scholar 

  11. Slade, D. Genes Dev. 34, 360–394 (2020).

    Article  CAS  Google Scholar 

  12. Beavis, P. A. et al. J. Clin. Invest. 127, 929–941 (2017).

    Article  Google Scholar 

  13. Giuffrida, L. et al. Nat. Commun. 12, 3236 (2021).

    Article  CAS  Google Scholar 

  14. Kjaergaard, J. et al. J. Immunol. 201, 782–791 (2018).

    Article  CAS  Google Scholar 

  15. Bahl, K. et al. J. Immunol. 176, 4284–4295 (2006).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

P.A.B. is supported by a Victorian Cancer Agency Mid-Career Fellowship (MCRF20011).

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Correspondence to Paul A. Beavis.

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Munoz, I., Beavis, P.A. PARP11 interfer(on)es with CAR T cell efficacy. Nat Cancer 3, 790–792 (2022). https://doi.org/10.1038/s43018-022-00406-w

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