Local C3 protein boosts cancer immunotherapy
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- Complement C3 produced within tumor tissue prevents immunosuppressive myeloid cells from entering the tumor microenvironment, improving the efficacy of immunotherapy, while circulating C3 from the liver has no impact.
- Yuki Miyai and team at Nagoya University found that disabling C3 production in cancer-associated fibroblasts reduced immunotherapy effectiveness in mice, even when blood C3 levels remained nearly normal.
- Anti-PD-1 immunotherapy became significantly more effective in mice when local C3 was present, and a drug mimicking C3’s action helped overcome resistance in previously unresponsive tumors.
- Lung cancer patients with high levels of C3 in tumor-adjacent tissue had better treatment responses and longer survival, while those with low local C3 showed no response—regardless of systemic C3 levels.
- Nagoya University researchers plan to test methods for increasing intratumoral C3 and determine optimal treatment timing, based on their findings published in Nature Communications.
Why it matters: Half of lung cancer patients in the study with high local C3 responded to immunotherapy, while none with low levels did—meaning measuring C3 in tumor tissue could soon guide treatment decisions and improve outcomes for patients with resistant cancers.
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