TY  - JOUR
AU  - Kanaan, Manal Hadi Ghaffoori
AU  - Lee, Beom-Jin
AU  - Abdullah, Sura Saad
AU  - Park, Chulhun
AU  - Ghasemian, Abdolmajid
AU  - Mudenda, Steward
PY  - 2026
DA  - 2026/01/14
TI  - Stem Cell-Derived Exosomes: Non-Coding RNA Cargos for Reprogramming the Tumor Immune Microenvironment
JO  - OBM Genetics
SP  - 325
VL  - 10
IS  - 01
AB  - Stem cell-derived exosomes (SDEs) have emerged as revolutionary mediators in cancer immunotherapy, offering unprecedented potential to reprogram the immunosuppressive tumor immune microenvironment (TIME). These nano-sized extracellular vesicles, laden with non-coding RNAs (ncRNAs), serve as natural biocompatible carriers, capable of orchestrating immune cell dynamics, stromal remodeling, and tumor cell fate. Unlike their tumor-derived counterparts, which often propagate oncogenic signals, SDEs uniquely harbor immunomodulatory miRNAs (e.g., miR-155, miR-342-3p) and lncRNAs (e.g., MALAT1, XIST) that recalibrate TIME components, activating cytotoxic CD8+ T cells, polarizing macrophages toward anti-tumor M1 phenotypes, and suppressing regulatory T cells (Tregs). This review delineates how SDEs leverage ncRNA cargo to dismantle immunosuppressive barriers: by silencing checkpoint molecules (PD-L1), reversing chemoresistance, and rewiring cancer-associated fibroblasts (CAFs). We highlight the dual roles of exosomal ncRNAs, such as miR-126, which initially bolster cancer stemness but, upon sustained delivery, trigger tumor-selective necroptosis, underscoring their context-dependent therapeutic utility. Despite promising preclinical outcomes, challenges in scalable production, off-target effects, and tumor heterogeneity necessitate engineered solutions, CRISPR-edited exosomes, surface-targeted modifications, and combinatorial regimens with checkpoint inhibitors. By integrating mechanistic insights with translational advances, this review positions SDEs as a paradigm-shifting tool in precision oncology and advocates for multidisciplinary strategies to harness their full potential. As the field evolves, SDE-based therapies stand poised to redefine cancer treatment, transforming the TIME from a fortress of immune evasion into a battleground for tumor eradication.
SN  - 2577-5790
UR  - https://doi.org/10.21926/obm.genet.2601325
DO  - 10.21926/obm.genet.2601325
ID  - Kanaan2026
ER  -