IL-26, a non-canonical mediator of DNA inflammatory stimulation, promotes TNBC engraftment and progression in association with neutrophils.
Interleukin-26 (IL-26) is a unique amphipathic member of the IL-10 family of cytokines that participates in inflammatory signaling through a canonical receptor pathway. It also directly binds DNA to facilitate cellular transduction and intracellular inflammatory signaling. While IL-26 has almost no described role in cancer, our in vivo screen of inflammatory and cytokine pathway genes revealed IL-26 to be one of the most significant inflammatory mediators of mammary engraftment and lung metastatic growth in triple-negative breast cancer (TNBC). Examination of human breast cancers demonstrated elevated IL-26 transcripts in TNBC specimens, specifically in tumor cells as well as in Th17 CD4+ T-cells within clinical TNBC specimens. IL-26 did not have an autocrine effect on human TNBC cells, but rather its effect on engraftment and growth in vivo required neutrophils. IL-26 enhanced mouse-derived DNA induction of inflammatory cytokines, which were collectively important for mammary and metastatic lung engraftment. To neutralize this effect, we developed a novel IL-26 vaccine to stimulate antibody production and suppress IL-26 enhanced engraftment in vivo, suggesting that targeting this inflammatory amplifier could be a unique means to control cancer-promoting inflammation in TNBC and other autoimmune diseases. Thus, we identified IL-26 as a novel key modulator of TNBC metastasis and a potential therapeutic target in TNBC as well as other diseases reliant upon IL-26-mediated inflammatory stimulation.
Trotter, Timothy N., Casey W. Shuptrine, Li-Chung Tsao, Robert D. Marek, Chaitanya Acharya, Jun-Ping Wei, Xiao-Yi Yang, et al. “IL-26, a non-canonical mediator of DNA inflammatory stimulation, promotes TNBC engraftment and progression in association with neutrophils.” Cancer Res, May 4, 2020. https://doi.org/10.1158/0008-5472.CAN-18-3825.