An immune protein so ancient it predates blood circulation may hold a key to making cancer immunotherapy work in tumors that resist it, researchers report.
The protein is complement C3, part of an evolutionarily old immune system found even in sponges and jellyfish. Scientists at Nagoya University found that what mattered for immunotherapy wasn’t C3 circulating in the blood, but C3 produced locally, inside the tumor. “What determined the efficacy of the immunotherapy treatment was not the C3 in the blood, but the local C3 produced at the tumor site,” said researcher Yuki Miyai.
How it helps
When C3 breaks down within tumor tissue, it forms a fragment (iC3b) that blocks immune-suppressing myeloid cells from flooding into the tumor. With those suppressive cells kept out, checkpoint-inhibitor drugs (anti-PD-1 antibodies) can reach and attack the cancer more effectively. The team showed the effect in mice with controlled C3 production and in human lung-cancer samples; the study appeared in Nature Communications in August 2026.
Why it matters
Immunotherapy transforms outcomes for some cancers but fails in many patients. Local tumor C3 could become a marker to identify who is most likely to benefit — and a lever to make resistant tumors respond. The findings are preclinical, but they add a fresh angle to a central problem in oncology.