Local C3 Protein Boosts Cancer Immunotherapy — SkimNews
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- Complement C3 produced within tumor tissue prevents immunosuppressive myeloid cells from entering the tumor microenvironment, improving the success of immunotherapy in mice.
- Nagoya University researchers discovered that only locally produced C3 — not C3 circulating in the blood — determines the efficacy of anti-PD-1 immunotherapy, as shown in mouse models with 90% reduced liver-derived C3.
- Yuki Miyai and team found that when cancer-associated fibroblasts stop producing C3 locally, immunotherapy effectiveness drops despite only a 9% decrease in total C3 levels.
- A drug mimicking C3’s action enabled immunotherapy to work in previously resistant tumors, significantly extending survival in mouse models.
- Lung cancer patient samples showed that high local C3 levels correlated with treatment response and longer survival, while blood C3 levels showed no such link.
Why it matters: Patients with C3-deficient tumors currently unresponsive to immunotherapy may gain new treatment options if therapies that boost local C3 prove effective in humans, shifting focus from systemic to targeted immune modulation with a protein evolutionarily older than blood circulation itself.
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