Priming the Tumor Immune Microenvironment Improves Immune Surveillance of Cancer Stem Cells and Prevents Cancer Recurrence

images[3]Here, we report that Tumor-associated macrophages (TAMs) promote Cancer stem cell (CSC) -like phenotypes in murine breast cancer cells by up regulating their expression of Sox-2, resistance to chemotherapy, and increased tumorigenicity. Down regulation of Sox-2 in tumors blocked the ability of TAMs to induce these CSC-like phenotypes and inhibited tumor growth. We identified a novel EGFR/ Stat3/Sox-2 paracrine signaling pathway between macrophages and breast cancer cells and showed that this crosstalk was effectively blocked by small molecule inhibitors AG1478 or CDDO-Im against EGFR and Stat3, respectively. Therefore, our study identifies a novel role for TAMs in breast CSC regulation and establishes a rationale for targeting the EGFR/Stat3/Sox-2 signaling pathway for CSC therapy. Intratumoral injection of miR-19a-3p impaired the capacity of breast tumor cells to migrate and invade, suggesting it to play a critical role in induction of macrophage polarization and to be a useful therapeutic target for remodeling the tumor immune environment and thereby improve treatment of breast cancer. Personal Author R. A. Reisfeld Y. Luo For more info go to: http://www.ntis.gov/search/product.aspx?ABBR=ADA594027 or call NTIS 1-800-553-6847 Mon – Fri 8am – 5pm est

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