Juntendo University researchers link IL-26 to colorectal cancer immunotherapy resistance

Researchers have identified a molecular mechanism that allows colorectal cancer to evade immune system attacks and develop resistance to PD-1 immunotherapy. A study led by Takumi Itoh at Juntendo University, published in Nature Communications, highlights the role of the inflammatory cytokine interleukin (IL-26).

Unlike many other cytokines that act as external signals, IL-26 appears to enter the nuclei of cancer cells, triggering epigenetic reprogramming. This process alters gene activity without changing the DNA itself, reshaping the tumor microenvironment to favor cancer growth. Specifically, the research found that IL-26 promotes a cellular state that recruits neutrophils, which in turn suppress the CD8+ T cells responsible for fighting the tumor. This mechanism explains why many patients initially responding to immune checkpoint inhibitors eventually develop resistance.