Immature myeloid cells directly contribute to skin tumor development by recruiting IL-17–producing CD4+ T cells

• DOI: 10.1084/jem.20140835
• Publication Date: 2015-02-10T06:16:04Z
• Authors: Myrna L. Ortiz; Vinit Kumar; Anna Martner; Sridevi Mony; Laxminarasimha Do...; Thomas Condamine; John Seykora; Stella C. Knight; George Malietzis; Gui Han Lee; Morgan Moorghen; Brianna Lenox; Noreen Luetteke; Esteban Celis; Dmitry Gabrilovich
• Keywords: CD4-Positive T-Lymphocytes; Skin Neoplasms; 610; Mice, Transgenic; Colitis; Article; 3. Good health; 03 medical and health sciences; Cell Transformation, Neoplastic; 0302 clinical medicine; Animals; Calgranulin B; Humans; Tetradecanoylphorbol Acetate; Female; Myeloid Cells; Chemokine CCL4

Evidence links chronic inflammation with cancer, but cellular mechanisms involved in this process remain unclear. We have demonstrated that humans, inflammatory conditions predispose to development of skin and colon tumors are associated accumulation tissues CD33+S100A9+ cells, the phenotype typical for myeloid-derived suppressor cells cancer or immature myeloid (IMCs) tumor-free hosts. To identify direct role these tumor development, we used S100A9 transgenic mice create topical absence infection tissue damage. These granulocytic IMCs upon application 12-O-tetradecanoylphorbol-13-acetate (TPA), resulting a dramatic increase formation papillomas during epidermal carcinogenesis. The effect on tumorigenesis was not immune suppression, CCL4 (chemokine [C-C motif] ligand 4)-mediated recruitment IL-17–producing CD4+ T cells. This chemokine released by activated IMCs. Elimination blockade IL-17 abrogated caused Thus, study implicates as an initial step facilitation formation, followed