by ecancer reporter Janet Fricker

The protein interleukin 22 (IL-22) plays a pivotal role in colon cancer metastasis, reports a study in Immunity.

The international collaboration of researchers from the US, China and Poland showed that IL-22 blockade in mouse models slowed cancer growth, while IL-22 addition made cells replicate more rapidly, and that these effects were mediated through an epigenetic factor called DOT1L.

“If you want to control cancer stem cells through new therapies, then you need to understand what controls the cancer stem cells,” says senior study author Weiping Zou, from the University of Michigan Medical School.

Given the known protective role of IL-22 in epithelial cells and its effects on bacteria, the team hypothesised that colon cancer infiltrating IL-22 cells might contribute to cancer stem cell renewal and expansion, and affect outcomes of patients.

First in patients they showed that high amounts of IL-22 mRNA were detected in primary colon cancer tissues compared to peripheral blood and colon tissue adjacent to the cancer.

Next they went on to demonstrate that both activation of the transcription factor STAT3 and epigenetic factor DOT1L were essential for IL-22-induced cancer stem cells.

The amount of DOT1L expression in colon cancer, they found, was an independent predictor of poor patient survival.

DOT1L may be a marker for colon cancer progression, and targeting this pathway, the authors suggest, could provide a new approach to colon cancer treatment.

Similar mechanisms, they add, may apply for other types of human cancers.

Reference

I Kryczek. Y Lin, N Nagarsheth, et al. IL-22 CD4 T Cells Promote Colorectal Cancer Stemness via STAT3 Transcription Factor Activation and Induction of the Methyltransferase DOT1L. Immunity 2014, 40: 772–784.