GSE158755
RNA sequencing data of differentially treated  cancer associated fibroblast, myeloid-derived supression cells, and ICC tumor cells in ICC patient
An interactive tumor microenvironment with different stromal cell types is necessary for supporting cancer stemness. Cancers with dense fibrotic stroma such as intrahepatic cholangiocarcinoma (ICC) are often highly aggressive and chemotherapy resistance. Here, we show that cancer associated fibroblasts (CAF) greatly enhances the capacity of blood CD33+ myeloid-derived suppressor cells (MDSCs) to promote stem-like properties in ICC cells and tumor growth via paracrine signaling. Mechanistically, CAF mediates hyperactivated 5-LO pathway in CD33+ MDSCs via secretion of IL-6 and IL-33, resulting in overproduction of LTB4, which acts on BLT2 to promote cancer stemness via Akt-mTOR signaling. hyperactivated 5-LO pathway are observed in tumor-infiltrating CD33+ MDSCs compared with blood counterparts from the same ICC patients. Moreover, BLT2 blockade augments chemotherapeutic efficacy in ICC PDX models. Thus, our study reveals a previously unrecognized stromal cell network in which CAF educate myeloid cells to shape the optimal supportive microenvironment for the aggressive nature of ICC. Overall design: Transcription files of blood CD33+MDSCs, tumor CD33+MDSCs, ICC tumor cells, cancer associated fibroblasts (CAFs), FAPkdCAFs, and blood CD33+MDSCs treated with conditional media of FAPkdCAFs or CAFs.