Local complement C3 boosts cancer immunotherapy

Researchers at Nagoya University in Japan discovered that complement C3 protein, when produced locally within tumors, prevents immunosuppressive myeloid cells from infiltrating the tumor microenvironment, thereby enhancing the efficacy of cancer immunotherapy. The findings, published in Tata Communications, show that circulating C3 in the blood does not influence treatment outcomes. In mouse models, reducing liver-produced C3 by 90% did not affect the effectiveness of anti-PD-1 antibody therapy, but stopping fibroblast-produced C3 within tumors reduced treatment efficacy. A drug mimicking C3's blocking effect enabled immunotherapy to work in resistant tumors and extended survival in mice. Analysis of lung cancer patient samples revealed that higher local C3 levels correlated with better treatment responses and longer survival, while blood C3 levels showed no correlation. The study suggests that boosting local C3 production could improve immunotherapy outcomes and help identify patients most likely to benefit.