Retinoic acid inhibits tumor-associated mesenchymal stromal cell transformation in melanoma

Bone marrow mesenchymal stem/stromal cells (BMSCs) can be transformed into tumor-associated MSCs (TA-MSCs) within the tumor microenvironment to facilitate tumor progression. However, the underline mechanism and potential therapeutic strategy remain unclear. Here, we explored that interleukin 17 (IL-17) cooperating with IFNγ transforms BMSCs into TA-MSCs, which promotes tumor progression by recruiting macrophages/monocytes and myeloid-derived suppressor cells (MDSCs) in murine melanoma. IL-17 and IFNγ transformed TA-MSCs have high expression levels of myelocyte-recruiting chemokines (CCL2, CCL5, CCL7, and CCL20) mediated by activated NF-κB signaling pathway. Furthermore, retinoic acid inhibits NF-κB signaling, decreases chemokine expression, and suppresses the tumor-promoting function of transformed TA-MSCs by prohibiting the recruitment of macrophages/monocytes and MDSCs in the tumor microenvironment. Overall, our findings demonstrate that IL-17 collaborating with IFNγ to induce TA-MSC transformation, which can be targeted by RA for melanoma treatment. RNAs were extracted from two biological replicates of cultured from wild-type BMSC incubated with control and 1μM ATRA , digested with DNAse I (AM2222, Ambion) and purified with Rneasy MinElute Spin Columns (Qiagen). TruePrepTM DNA library Prep Kit V2 (Vazyme, TD503) was used to prepare RNA seq library following the manufacturer’s protocol. DNA library sequenced by Illumina HiSeq 2500 platform.