CLL-cell-mediated MDSC induction by exosomal miR-155 transfer is disrupted by vitamin D

The role of cancer-derived microRNAs in cancer immune escape

“…However, this exosomal-mediated MDSCs induction could be interfered by additional vitamin D treatment. Analogously, Bruns et al found that chronic lymphocytic leukemiaderived miR-155 induced the formation of MDSCs but this process was hampered by vitamin D treatment [137].…”

“…Immunosuppressive [125] miR-24-3p NPC Immunosuppressive [126] miR-891a NPC Immunosuppressive [126] miR-106a-5p NPC Immunosuppressive [126] miR-20a-5p NPC Immunosuppressive [126] miR-1908 NPC Immunosuppressive [126] TAMs miR-222-3p EOC Immunosuppressive [127] miR-940 EOC Immunosuppressive [128] miR-21-3p EOC Immunosuppressive [129] miR-125b-5p EOC Immunosuppressive [129] miR-181d-5p EOC Immunosuppressive [129] miR-21 Head and neck cancer Immunosuppressive [130] miR-1246 Colon cancer Immunosuppressive [131] miR-16 Breast cancer Immunostimulatory [132] MDSCs miR-107 Gastric cancer Immunosuppressive [133] miR-21 OSCC Immunosuppressive [134] miR-21 Glioma Immunosuppressive [135] miR-10a Glioma Immunosuppressive [135] miR-29a Glioma Immunosuppressive [136] miR-92a Glioma Immunosuppressive [136] miR-155 CLL Immunosuppressive [137] CAFs miR-27a Gastric cancer Immunosuppressive [138] miR-1247-3p HCC Immunosuppressive [139] miR-21 HCC Immunosuppressive [140] NPC nasopharyngeal carcinoma, TAM tumor-associated macrophage, EOC epithelial ovarian cancer, MDSC myeloid-derived suppressor cell, OSCC oral squamous cell carcinoma, CLL chronic lymphocytic leukemia, CAF cancer-associated fibroblast, HCC hepatocellular carcinoma M2-like phenotype and suppressing the expression of M1 phenotype-associated markers [130]. Similarly, Cooks et al observed that cancer cells harboring TP53 mutation could reprogram neighboring TAMs into pro-tumor state via secreting miR-1246-enriched exosomes [131].…”

Exosomal miRNAs in tumor microenvironment

“…In the research of glioblastoma, exosomal miR-10a targets RORA and affects the differentiation of MDSCs through the NFκB pathway, exosomal miR-21 targets PTEN and affects the activation of MDSCs via the p-STAT3/p-p65/p-Akt pathway [165]. Exosomal miR-155 istransmitted to monocytes, leading to nuclear translocation of NFkB and phosphorylation of STAT1, reprograming conventional monocytes into MDSCs [166]. Changes in the function of MDSCs affect the progression of the tumor itself.…”

Role of Non-Coding RNAs in the Development of Targeted Therapy and Immunotherapy Approaches for Chronic Lymphocytic Leukemia

“…MDSCs are generated in the bone marrow and, in tumor-bearing hosts, migrate to the tumor site to support the establishment of the TME [75]. Bruns et al showed that miR-155 delivered by CLL-EV to MDSC for induction can be disrupted by vitamin D [76].…”

“…Interestingly, recent observations from preclinical models suggest that the transfer of miR-155 via EVs may also contribute to CLL-mediated myeloid-derived suppressor cells (MDSC) induction. MDSC have a key role in the immune suppressive networks in the TME, and the modulation of the TME is under evaluation as a possible strategy for cancer treatment [75,76]. In addition, an inhibitor of miR-155, (MRG-106), was developed for the treatment of blood cancers (www.miRagen.com) and it is currently under investigation for safety and tolerability in CLL patients (NCT02580552).…”