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| Status |
Public on Sep 21, 2018 |
| Title |
Intracellular activation of complement C3 leads to PD-L1 antibody treatment resistance via modulating tumor-associated macrophages |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Mounting evidence has highlighted the importance of complement in the construction of an immunosuppressive tumor microenvironment (TME). Tumor cell-derived C3 has been previously reported, however, whether and how it acts on anti-tumor immunity remains to be elucidated. Here, we describe a unique role of tumor cell-derived C3 in suppressing anti-tumor immunity. Tumor cell-derived C3 was activated intracellularly, which results in generation of C3a. C3a could modulate tumor-associated macrophages (TAMs) via C3a-C3aR-PI3Kγ signaling, thereby repressing anti-tumor immunity. More importantly, deletion of C3 in tumor cells with high C3 expression is sufficient to enhance the efficacy of ɑPD-L1 treatment. Collectively, our present results suggest tumor cell-derived C3 may serve as a novel target in cancer immunotherapy, specifically targeting C3 in tumor cells to enhance anti-tumor immunity.
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| Overall design |
Tumor-associated macrophages were isolated from CT26 Sg-Con or CT26 Sg-C3 tumors on day 15 post tumor challenge. The RNA were quantified by RNA-seq.
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| Contributor(s) |
Zha H, Zhu B |
| Citation missing |
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| BioProject |
PRJNA491338 |
| Submission date |
Sep 20, 2018 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Haoran Zha |
| E-mail(s) |
zhahaoran@tmmu.edu.cn
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| Organization name |
Institute of Cancer, Xinqiao Hospital,Third Military Medical University
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| Street address |
Shaping Street #31
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| City |
Chongqing |
| ZIP/Postal code |
400037 |
| Country |
China |
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| Platforms (1) |
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| Samples (6)
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| Relations |
| SRA |
SRP161917 |
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