Recruitment of CCR2⁺ tumor associated macrophage to sites of liver metastasis confers a poor prognosis in human colorectal cancer.

ABSTRACT: The tumor microenvironment (TME) represents a significant barrier to creating effective therapies for metastatic colorectal cancer (mCRC). In several malignancies, bone marrow derived CCR2⁺ inflammatory monocytes (IM) are recruited to the TME by neoplastic cells, where they become immunosuppressive tumor associated macrophages (TAM). Here we report that mCRC expression of the chemokine CCL2 facilitates recruitment of CCR2⁺ IM from the bone marrow to the peripheral blood. Immune monitoring of circulating monocytes in patients with mCRC found this influx was a prognostic biomarker and correlated with worse clinical outcomes. At the metastatic site, mCRC liver tumors were heavily infiltrated by TAM, which displayed a robust ability to dampen endogenous anti-tumor lymphoc

SUBMITTER: Grossman JG 

PROVIDER: S-EPMC6140580 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature