Ancient Immune Protein C3 Could Transform Cancer Immunotherapy
Scientists discovered that an evolutionarily ancient protein called C3, when produced inside tumors, blocks immune-suppressing cells and makes cancer immunotherapy more effective. Recreating this effect could help patients whose tumors don't naturally produce enough C3.
Breakthrough in Cancer Treatment
A protein that evolved long before the human circulatory system may help unlock stronger cancer treatments. Scientists at Nagoya University in Japan discovered that complement C3 can prevent immune-suppressing cells from building up inside tumors, but only when the protein is produced locally within the tumor.
How C3 Works
C3 is an evolutionarily ancient protein found even in simple animals such as sponges and jellyfish. Most C3 is made in the liver and released into the bloodstream, where it helps the immune system defend the body against infections. However, C3 traveling through the bloodstream did not influence how well treatment worked.
The key finding centers on local C3 production. The researchers found that C3 made inside tumor tissue prevents immunosuppressive myeloid cells from entering the tumor microenvironment, the area surrounding and supporting cancer cells. By limiting these cells, local C3 gives the immune system a better opportunity to attack the cancer. Higher C3 was linked to better outcomes with cancer immunotherapy.
Clinical Implications
Researchers were even able to recreate this effect in resistant tumors, significantly improving survival in mice. They used a drug that imitates the way C3 blocks myeloid cells from entering tumors. The combination made previously resistant tumors respond to immunotherapy and significantly prolonged survival in mice.
The findings, published in Nature Communications, suggest that reproducing this local effect could benefit patients whose tumors do not produce enough C3 naturally. This discovery opens new avenues for treating patients with immunotherapy-resistant cancers and may help identify which patients are most likely to benefit from immunotherapy.