Targeting inflammatory monocytes in human metastatic colorectal cancer.

605Background: Colorectal cancer (CRC) is the most common gastrointestinal malignancy. 60% of CRC patients are diagnosed with metastatic CRC (mCRC) and the 5-year survival is u003c 20%. CCR2+ inflammatory monocytes (IM) are recruited from the bone marrow to the tumor microenvironment by the CCL2/CCR2 chemokine axis. At the tumor, they become tumor associated macrophages (TAM) and play a crucial role in promoting tumor progression, metastasis, and chemoresistance. While the importance of IM has been shown in other malignancies, little is known about their role in mCRC. Methods: Flow cytometry was performed on human and murine PBMCs, adjacent normal tissue, and tumors. Qualitative RT-PCR, ELISA, and confocal microscopy were performed for CCL2 expression. T-cell suppression assays were performed using CD14+ IM isolated from patient PBMCs and liver metastasis (LM). A murine model of CRC LM was created by hemispleen injection of luciferase-labelled MC38 CRC cells. Mice were treated with a CCR2 inhibitor and/or FOL...