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

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Zha, H; Han, X; Zhu, Y; Yang, F; Li, Y; Li, Q; Guo, B; Zhu, B

Published Date

  • 2017

Published In

Volume / Issue

  • 6 / 10

Start / End Page

  • e1349587 -

PubMed ID

  • 29123963

Pubmed Central ID

  • 29123963

International Standard Serial Number (ISSN)

  • 2162-4011

Digital Object Identifier (DOI)

  • 10.1080/2162402X.2017.1349587

Language

  • eng

Conference Location

  • United States