Stromal derived interleukin-6 drives epithelial-to-mesenchymal transition and therapy resistance in esophageal adenocarcinoma
In the paper, Ebbing and colleagues (from the Bijlsma and Van Laarhoven groups) show that cancer-associated fibroblasts, the most abundant noncancer cell type in esophageal cancer tissue, contribute to the resistance of tumors against most currently applicable treatments. These cancer-associated fibroblasts do so by producing and secreting the inflammatory protein IL-6. IL-6 induces a mesenchymal, resistant tumor cell state. Inhibition of IL-6 reverted the mesenchymal cell state and resensitized tumor cells to therapy. Blood-based markers for the presence of IL-6–producing fibroblasts were identified and found to be predictive for the response to neoadjuvant therapy.
Ebbing EA, Van der Zalm AP, Steins A, Creemers A, Hermsen S, Rentenaar R, Klein M, Waasdorp C, Hooijer GKJ, Meijer SL, Krishnadath KK, Punt CJA, Van Berge Henegouwen MI, Gisbertz SS, Van Delden OM, Hulshof MCCM, Medema JP, Van Laarhoven HWM*, Bijlsma MF*
Stromal derived interleukin-6 drives epithelial-to-mesenchymal transition and therapy resistance in esophageal adenocarcinoma.
Proceedings of the National Academy of Sciences of the United States of America. Published ahead of print January 22, 2019 https://doi.org/10.1073/pnas.1820459116