Nagoya University study identifies key role of C3 protein in cancer immunotherapy

Researchers at Nagoya University have discovered that the ancient immune protein complement C3 may play a critical role in enhancing the effectiveness of cancer immunotherapy. The study, published in Nature Communications, reveals that the location of C3 production is more significant than its concentration in the bloodstream.

While most C3 is produced by the liver and circulates in the blood, the study found that C3 produced locally within tumor tissue by cancer-associated fibroblasts is what drives therapeutic success. When C3 is produced inside the tumor, it breaks down into a fragment called iC3b, which prevents immunosuppressive myeloid cells from infiltrating the tumor environment. This allows immune checkpoint inhibitors to work more effectively by preventing the buildup of cells that typically interfere with the body's ability to attack cancer.

In mouse models, inhibiting the C3 produced within the tumor significantly reduced the efficacy of immunotherapy, even when blood C3 levels remained largely unchanged. Clinical analysis of lung cancer patients supported these findings, showing that higher concentrations of C3 around the tumor correlated with better treatment responses and survival rates, whereas blood C3 levels showed no such correlation.