Existing Immune Protein May Boost Immunotherapy Against Cancer

Nagoya University researchers have discovered an ancient protein that occurs naturally in a wide variety of animals and has the potential to make immunotherapy treatments more effective. C3, a protein produced in the liver, typically helps the body fight off infections. However, when the protein is produced by cells within a tumor, it seems to act against immunosuppressive cells, making tumors more susceptible to immunotherapy.

The researchers believe inducing C3 creation in tumors with low C3 levels could make immunotherapy more effective at eradicating cancerous cells from the body. Lead study author Yuki Miyai, an assistant professor at Nagoya University’s Graduate School of Medicine, notes that until his team published its findings in the journal Nature Communications, the role played by complement C3 in tumors was unknown.

Most of the C3 in the tumor’s vicinity is produced by fibroblasts, the normal healthy cells that surround cancer tumors. According to the researchers, C3 produced within tumor tissue blocks immunosuppressive myeloid cells from intruding into the tumor microenvironment. Keeping them out of the tumor prevents the development of an immunosuppressive environment that shields tumors from the immune system, making them much more susceptible to cancer treatments like immunotherapy.

Theoretically, flooding tumors with complement C3 could be the key to making immunotherapy much more effective against several types of cancers that have consistently proven to be hard to treat. The researchers reached this tentative conclusion after they used mice to determine the effect of C3 produced in tumorous cells. They found that while depriving the mice of liver-produced C3 didn’t affect immune function, stopping C3 production within the tumor by just 9% reduced immunotherapy efficacy.

Miyai says C3 produced locally breaks down into a fragment that keeps myeloid cells, which lead to immunosuppressive environments in cancerous cells, from entering tumors. Without an environment that actively suppresses the immune system, tumors become more sensitive to immunotherapy treatment.

Tests to see if C3’s effects could be reproduced in cancers that have historically resisted immunotherapy were largely successful, opening the door to more effective treatments for patients diagnosed with hard-to-treat cancers.

The tests employed a drug that can imitate C3’s myeloid cell-blocking capabilities, but the researchers are more interested in approaches to increasing C3 levels in tumors. Figuring out possible methods and determining optimal C3 treatment times will guide their future research efforts. The research team also believes it could gain deeper insight into additional processes that affect immune regulation by studying C3’s local activity in tumors.

It would be interesting to hear what entities like Calidi Biotherapeutics Inc. (NYSE American: CLDI) that are also engaged in developing immunotherapies think about the role that C3 can play in boosting the fight against cancer either on its own or in conjunction with existing immune system therapies.

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