Abstract LB-127: Identifying an IDO-expressing “fibrocyte” subset of myeloid suppressor cells in pediatric cancer patients

Abstract

Abstract Human myeloid derived suppressor cells (MDSC) have been described as CD14-CD11b+CD33+HLADR- cells that exert T cell suppression via ROS, ARG1 and iNOS2. Here, we report a novel myeloid subset found within mononuclear fraction elutriated from apheresis samples of pediatric cancer patients vs. healthy controls. Of 60 pediatric cancer patients studied, we frequently observed expanded numbers of CD14-CD123-CD11chi cells, which were rare and found only at low levels in healthy donors. Like previously described MDSC, these cells were CD11b+, but CD33lo/-HLADR+. In addition, these abnormal myeloid cells were CD34+CD15+CD16+CD66b+CD68+PDL1+ and IL4Rα+. Interestingly they also expressed α smooth muscle actin and collagen I/V on their surface, which are hallmarks of fibrocytes. The fibrocytes expressed high levels of indoleamine oxidase (IDO), but did not express ARG1, ARG2, iNOS2. They suppressed T cell proliferation in response to OKT3, which was partially reversed by the addition of 1MT, an inhibitor of IDO. Given the IL4Rα expression, we sought to induce these cells in vitro from normal monocytes using IL-4. Indeed, IL4 alone was sufficient to drive monocytes to differentiate into fibrocytes, which demonstrate a spindle-like shape, adhere to plastic, acquire the CD11chiCD14-CD34+CD16+collagenI+ phenotype, and express IDO. Fibrocytes have previously been implicated in chronic inflammation, angiogenesis and wound healing. We conclude that they also constitute a novel subset of myeloid derived suppressor cells in cancer patients, and could contribute to tumor progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-127. doi:1538-7445.AM2012-LB-127