Unlocking the Potential of an Ancient Immune Molecule

An ancient immune molecule, complement C3, has been discovered to hold the key to transforming cancer immunotherapy. This protein, which has been present in evolution long before blood circulation, may help turn stubborn, treatment-resistant tumors into targets for cancer immunotherapy.

Researchers at Nagoya University in Japan have made a groundbreaking discovery that sheds new light on the role of complement C3 in cancer treatment. The team found that locally produced C3 within tumor tissue prevents immunosuppressive myeloid cells from entering the tumor microenvironment. These cells can weaken the body’s ability to attack cancer, giving the immune system a better opportunity to recognize and fight tumor cells.

The researchers conducted experiments in mice to distinguish between C3 from different sources. They found that when the amount of liver-produced C3 was reduced by 90%, an immunotherapy drug (anti-PD-1 antibody) remained just as effective as it was in mice with normal C3 levels. However, when researchers stopped fibroblasts inside the tumor from producing C3, the same treatment became less effective, even though the amount of circulating C3 fell by only a small amount (a 9% decrease).