Results showed that xenografted Mino along with CD14+ monocytes significantly increased the tumor growth in vivo compared with MCL cells alone (P < .001), whereas treatment with liposomal clodronate (to deplete the macrophages) reversed the effect of CD14+ monocytes on growth of MCL xenografts (P < .001). Mechanistically, IL-10 secreted by MCL-polarized M2-like macrophages was found to be responsible for increasing MCL growth by activating STAT1 signaling, whereas IL-10 neutralizing antibody or STAT1 inhibition by fludarabine or STAT1 short hairpin RNA significantly abolished MCL growth (P < .01). Collectively, our data show the existence of a tumor microenvironmental network of macrophages and MCL tumor and suggest the importance of macrophages in interventional therapeutic strategies against MCL and other lymphoid malignancies.
Moreover, our data suggest that a higher proportion of microglia may be beneficial for patient survival in glioblastoma. Accordingly, this tissue-based method for myeloid population differentiation could serve as a useful prognostic tool.
CCL2, CCR2, CSF1R and CD163 expression in macrophages was dependent on active MCSFR signaling as shown by M-CSFR inhibition. These results indicate that colon fibroblasts and not TCs are the major cellular component, recruiting and dictating the fate of infiltrated monocytes towards a specific macrophage population, characterized by high CD163 expression and CCL2 production.
In contrast, we found that a limited subgroup of NE-low tumors is immune-deserted and express distinct cellular pathways from NE-high tumors. Furthermore, we identified potential molecular targets based on our expression data in NE-low and immune-oasis tumor subsets, including CD70, ANXA1, ITGB6, TP63, IFI27, YBX3 and CXCR2.
Moreover, ERK1/2 phosphorylation was associated with the CCL20-driven induction of CD163 expression in THP-1. Tongue cancer cell-derived CCL20 that was induced by interaction with macrophages promotes CD163 expression on macrophages.
Based on the ESTIMATE algorithm, we obtained and characterized prognosis-related genes in the TME of ESCC samples from the TCGA database. We have further revealed that C3AR1 may cause an immunosuppressive microenvironment by affecting the polarization of macrophages to M2 phenotype and lead to the progression of ESCC, which indicates that C3AR1 may be a potential target for immunotherapy.
By immunohistochemistry, bone marrow levels of pSTAT3 were increased specifically within CD163 cells in both MGUS and MM patients.In conclusion, macrophage-related inflammatory changes, including activation of STAT3, were present already at the MGUS stage, at similar levels as in MM. Specific increase in pSTAT3 levels within CD163 cells supports that the CD163 scavenger receptor may be a useful target for future delivery of STAT3-inhibitory drugs to TAMs in MM patients.
2 months ago
CD163 (CD163 Molecule) • STAT3 (Signal Transducer And Activator Of Transcription 3) • MRC1 (Mannose Receptor C-Type 1)
We identify immune populations by manual gating and FlowSOM clustering with differential abundance in DLBCL and in those cases that subsequently relapsed, reflecting immune dysfunction associated with disease and outcome. Our data provide an explanation for the prognostic nature of the AMC /ALC, support the challenge to identify biomarkers and provide insight into steps that may be required to overcome the immune defects in RCHOP refractory DLBCL.