GSE144609 Expression data from cultured mouse bone-marrow monocytes.

Contributors : Samir Devalaraja ; Tsun K To ; Ian W Folkert ; Ramakrishnan Natesan ; M Z Alam ; Minghong Li ; Yuma Tada ; Konstantin Budagyan ; Mai Dang ; Li Zhai ; Graham P Lobel ; Gabrielle E Ciotti ; T S Eisinger-Mathason ; Irfan A Asangani ; Kristy Weber ; M C Simon ; Malay HaldarSeries Type : Expression profiling by arrayOrganism : Mus musculusRetinoic acid signaling regulates monocyte differentiation into dendritic cells or macrophages. We used microarrays to uncover gene expression changes associated with retinoic acid exposure in mouse monocytes.The immunosuppressive tumor microenvironment (TME) is a major barrier to immunotherapy. Within solid tumors, why monocytes preferentially differentiate into immunosuppressive tumor associated macrophages (TAMs) but not immunostimulatory dendritic cells (DCs) remains unclear. Using multiple murine sarcoma models, we found that the TME induced retinoic acid (RA) production by tumor cells, which polarized intratumoral monocyte differentiation towards TAMs and away from DCs via suppression of DC-promoting transcription factor Irf4. Genetic inhibition of RA production by tumor cells or pharmacologic inhibition of RA signaling within TME increased stimulatory monocyte-derived cells, enhanced T cell-dependent anti-tumor immunity and demonstrated striking synergy with immune checkpoint blockade. Further, RA responsive gene signature in human monocytes correlated with an immunosuppressive TME in multiple human tumors. RA has b...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Mus musculus Source Type: research