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Zha H, Han X, Zhu Y, et al. Blocking C5aR signaling promotes the anti-tumor efficacy of PD-1/PD-L1 blockade. Oncoimmunology. 2017;6(10):e1349587doi: 10.1080/2162402X.2017.1349587.
Zha, H., Han, X., Zhu, Y., Yang, F., Li, Y., Li, Q., Guo, B., & Zhu, B. (2017). Blocking C5aR signaling promotes the anti-tumor efficacy of PD-1/PD-L1 blockade. Oncoimmunology, 6(10), e1349587. https://doi.org/10.1080/2162402X.2017.1349587
Zha, Haoran, et al. "Blocking C5aR signaling promotes the anti-tumor efficacy of PD-1/PD-L1 blockade." Oncoimmunology vol. 6,10 (2017): e1349587. doi: https://doi.org/10.1080/2162402X.2017.1349587
Zha H, Han X, Zhu Y, Yang F, Li Y, Li Q, Guo B, Zhu B. Blocking C5aR signaling promotes the anti-tumor efficacy of PD-1/PD-L1 blockade. Oncoimmunology. 2017 Jul 13;6(10):e1349587. doi: 10.1080/2162402X.2017.1349587. eCollection 2017. PMID: 29123963; PMCID: PMC5665063.
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Oncoimmunology. 2017 Jul 13;6(10):e1349587. doi: 10.1080/2162402X.2017.1349587. eCollection 2017.

Blocking C5aR signaling promotes the anti-tumor efficacy of PD-1/PD-L1 blockade.

Oncoimmunology

Haoran Zha, Xiao Han, Ying Zhu, Fei Yang, Yongsheng Li, Qijing Li, Bo Guo, Bo Zhu

Affiliations

  1. Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, P.R. China.
  2. Chongqing Key Laboratory of Immunotherapy, Chongqing, P.R. China.
  3. Department of Immunology, Third Military Medical University, Chongqing, P.R. China.
  4. Department of Pathogenic Biology, Third Military Medical University, Chongqing, P.R. China.
  5. Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA.

PMID: 29123963 PMCID: PMC5665063 DOI: 10.1080/2162402X.2017.1349587

Abstract

Anti-PD-1/PD-L1 therapy has achieved great success in the clinic; however, only a small fraction of cancer patient benefit from PD-1/PD-L1 blockade therapy, and overcoming resistance to PD-1/PD-L1 blockade has thus become a primary priority. In this study, we demonstrated that administration of PD-1/PD-L1 antibodies resulted in the activation of the complement system and massive generation of C5a. Generation of C5a did not change the accumulation of MDSCs in either the tumor or spleen but enhanced their inhibitory potential. In addition, blockade of C5a-C5aR signaling in combination with PD-1/PD-L1 antibodies greatly enhanced the anti-tumor efficacy of PD-1/PD-L1 antibodies. Overall, these data indicate an immunosuppressive role of C5a in the context of PD-1/PD-L1 blockade therapy and provide a strong incentive to clinically explore combination therapies using a C5a antagonist.

Keywords: MDSCs; PD-1 treatment resistance; complement C5a; immune checkpoint blockade; tumor immunotherapy

References

  1. J Hepatol. 2015 Feb;62(2):354-62 - PubMed
  2. J Immunol. 2012 Apr 15;188(8):4032-42 - PubMed
  3. Sci Transl Med. 2016 Mar 2;8(328):328rv4 - PubMed
  4. Oncoimmunology. 2015 Feb 03;4(1):e954829 - PubMed
  5. Cancer Res. 2009 Aug 15;69(16):6367-70 - PubMed
  6. J Clin Invest. 2015 Sep;125(9):3356-64 - PubMed
  7. Immunol Rev. 2016 Nov;274(1):16-32 - PubMed
  8. Science. 2016 Jun 17;352(6292):aad1210 - PubMed
  9. Cancer Res. 2017 May 15;77(10 ):2607-2619 - PubMed
  10. Cancer Res. 2015 Jul 15;75(14 ):2928-36 - PubMed
  11. Cell Rep. 2014 Mar 27;6(6):1085-1095 - PubMed
  12. Cell Rep. 2015 Jul 14;12(2):244-57 - PubMed
  13. Nat Commun. 2016 Jul 06;7:12150 - PubMed
  14. Lung Cancer. 2013 Aug;81(2):259-65 - PubMed
  15. Oncoimmunology. 2014 Dec 15;3(10):e956579 - PubMed
  16. N Engl J Med. 2015 Nov 5;373(19):1803-13 - PubMed
  17. Cancer Res. 2014 Jul 1;74(13):3454-65 - PubMed
  18. J Clin Invest. 2014 Feb;124(2):687-95 - PubMed
  19. Br J Cancer. 2014 Sep 23;111(7):1391-9 - PubMed
  20. Cancer Discov. 2016 Sep;6(9):1022-35 - PubMed
  21. J Immunol. 2003 Aug 1;171(3):1581-7 - PubMed
  22. J Exp Med. 2014 May 5;211(5):781-90 - PubMed
  23. Nat Immunol. 2008 Nov;9(11):1225-35 - PubMed
  24. Immunol Lett. 2003 Jul 3;88(1):47-52 - PubMed
  25. Nature. 2014 Jun 19;510(7505):407-411 - PubMed
  26. Science. 1973 May 18;180(4087):713-6 - PubMed
  27. N Engl J Med. 2015 May 21;372(21):2018-28 - PubMed
  28. N Engl J Med. 2015 Jul 2;373(1):23-34 - PubMed
  29. J Immunol. 2012 Nov 1;189(9):4674-83 - PubMed
  30. Cancer Treat Rev. 2017 Jan;52:71-81 - PubMed
  31. Immunity. 2016 Jun 21;44(6):1255-69 - PubMed

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