Blocking C5aR signaling promotes the anti-tumor efficacy of PD-1/PD-L1 blockade
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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2017-10-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2017.1349587 |
| _version_ | 1818295158567862272 |
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| author | Haoran Zha Xiao Han Ying Zhu Fei Yang Yongsheng Li Qijing Li Bo Guo Bo Zhu |
| author_facet | Haoran Zha Xiao Han Ying Zhu Fei Yang Yongsheng Li Qijing Li Bo Guo Bo Zhu |
| author_sort | Haoran Zha |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T03:43:12Z |
| format | Article |
| id | doaj.art-84ed2460dae3431b87054a6f41f73078 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-13T03:43:12Z |
| publishDate | 2017-10-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-84ed2460dae3431b87054a6f41f730782022-12-22T00:00:53ZengTaylor & Francis GroupOncoImmunology2162-402X2017-10-0161010.1080/2162402X.2017.13495871349587Blocking C5aR signaling promotes the anti-tumor efficacy of PD-1/PD-L1 blockadeHaoran Zha0Xiao Han1Ying Zhu2Fei Yang3Yongsheng Li4Qijing Li5Bo Guo6Bo Zhu7Third Military Medical UniversityThird Military Medical UniversityThird Military Medical UniversityThird Military Medical UniversityThird Military Medical UniversityDuke University Medical CenterThird Military Medical UniversityThird Military Medical UniversityAnti-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.http://dx.doi.org/10.1080/2162402X.2017.1349587tumor immunotherapyimmune checkpoint blockadecomplement c5amdscspd-1 treatment resistance |
| spellingShingle | Haoran Zha Xiao Han Ying Zhu Fei Yang Yongsheng Li Qijing Li Bo Guo Bo Zhu Blocking C5aR signaling promotes the anti-tumor efficacy of PD-1/PD-L1 blockade OncoImmunology tumor immunotherapy immune checkpoint blockade complement c5a mdscs pd-1 treatment resistance |
| title | Blocking C5aR signaling promotes the anti-tumor efficacy of PD-1/PD-L1 blockade |
| title_full | Blocking C5aR signaling promotes the anti-tumor efficacy of PD-1/PD-L1 blockade |
| title_fullStr | Blocking C5aR signaling promotes the anti-tumor efficacy of PD-1/PD-L1 blockade |
| title_full_unstemmed | Blocking C5aR signaling promotes the anti-tumor efficacy of PD-1/PD-L1 blockade |
| title_short | Blocking C5aR signaling promotes the anti-tumor efficacy of PD-1/PD-L1 blockade |
| title_sort | blocking c5ar signaling promotes the anti tumor efficacy of pd 1 pd l1 blockade |
| topic | tumor immunotherapy immune checkpoint blockade complement c5a mdscs pd-1 treatment resistance |
| url | http://dx.doi.org/10.1080/2162402X.2017.1349587 |
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