The ability of cancerous cells to evade immune response can be instrumental in the growth of cancer within the body. For this reason, researchers examine the ways in which cancer is able to block a normal immune response and aim to develop immunotherapy drugs that target those mechanisms of action. In a new study published in Nature, researchers found that a vital immune protein called interleukin-18 (IL-18) was blocked by tumors, allowing the tumor to evade the human immune system. However, the researchers were able to find a synthetic form of IL-18, known as a decoy receptor, that was unaffected by the tumor’s blocking signals in studies.

Interleukin-18 is a pro-inflammatory protein that is part of the body’s cytokines. IL-18 works to mobilize the T cells and NK cells that attack and kill damaged or infected cells. A tumor that blocks the function of IL-18 can essentially continue to grow unchecked by the NK cells that would typically neutralize or inhibit tumor cells. Many tumors are particularly adept at evading IL-18 by releasing a protein that binds with IL-18 before it can reach the tumor.

Previous research tested IL-18 as an immunotherapeutic treatment for tumors, but this was ineffective because the IL-18 binding protein released by the tumor worked on both the natural IL-18 and the added IL-18 used in immunotherapy. The fact that added pro-inflammatory IL-18 resulted in no effect alerted researchers to the presence of IL-18 binding protein and motivated the search for a form of IL-18 that would be able to resist tumor-released IL-18 binding protein.

This new study by Yale researchers has tested a synthetic form of IL-18 with a specific mutation that prevents the tumor’s IL-18 binding protein from inhibiting the function of the IL-18. Scientists hope that this potential new treatment may work against tumors that have historically been resistant to immunotherapy. Researchers hope that clinical trials for this new form of IL-18 may begin next year.