Identifying mechanisms driving macrophage differentiation and function in colorectal cancer.

Abstract The tumor microenvironment (TME) plays a critical role in cancer proliferation, metastasis, & responses of patients to treatment. Within the TME, tumor-initiated signaling results aberrant activation stromal immune cell populations suppress surveillance, induce angiogenesis, establish premetastatic niches. Macrophages, subset antigen presenting myeloid cells, are most abundant TME participate regulation during tumorigenesis. They functionally exhibit both anti pro-tumorigenic properties as well demonstrate plasticity repolarize between phenotypes based on environmental cues. Additionally, macrophage predominance within tumors have been correlated favorable prognoses some cancers. However, there is lack consensus for their colorectal (CRC) progression. In this study, we investigated CRCs with distinct mutations, grade, origin ability drive differentiation function vitro. Human CRC cells were used create multicellular spheroids better recapitulate vivo biology. CD14 +monocytes polarized into subsets (M 0/M1/M2) by cytokine/growth-factor exposure (GMCSF/MCSF/IFNγ/IL4/IL6/IL10) co-cultured each model. Spheroid proliferation inflammatory profiles alone/in co-culture assessed live-cell microscopy, viability, multiplex assays. Macrophage polarization, spheroid infiltration, anti-tumor activity examined flow-cytometry, functional assessments. Overall, study demonstrates that it may be useful direct targeted therapies influence polarization patients. Supported funding from Janssen Pharmaceutical Companies Johnson Johnson, Inc. under direction DPDS Postdoctoral Fellowship Program and Biologics Discovery Division - Exploratory Biology Department.