Preclinical and Clinical Translation of Immunomodulatory Role of Mesenchymal Stem Cells in Cancer Therapy Era.

BACKGROUND

Mesenchymal stem cells (MSCs) are multipotent stromal cells with dual regenerative and immunomodulatory properties that have attracted growing attention in cancer therapy. Their inherent tumor-homing ability enables localized delivery of therapeutic agents, while their capacity to regulate both innate and adaptive immunity positions MSCs at the interface of stromal biology and cancer immunotherapy. However, MSC functions are highly context-dependent and vary across tumor types.

METHODS

This review summarizes preclinical and clinical evidence on the immunomodulatory roles of MSCs in cancer. Experimental studies and early-phase clinical trials involving unmodified, preconditioned, and genetically engineered MSCs, as well as MSC-derived extracellular vesicles, were evaluated.

RESULTS

Unmodified MSCs often promote immune evasion by expanding regulatory T cells, expressing checkpoint ligands, and secreting immunosuppressive and metabolic mediators, such as IDO, nitric oxide, and PGE2. In contrast, engineered or primed MSCs can redirect immune responses toward activation, enhancing NK- and T-cell cytotoxicity and enabling targeted delivery of cytokines, oncolytic viruses, and pro-apoptotic ligands. Early clinical trials generally demonstrate safety and feasibility; however, efficacy remains variable due to heterogeneity of MSC sources, manufacturing challenges, and lack of standardized potency assays. Notably, tumor-promoting effects have been reported under specific conditions.

CONCLUSION

MSCs Represent a highly plastic and programmable platform for immune modulation in cancer. Advances in genetic engineering and extracellular vesicle-based strategies may improve therapeutic efficacy while reducing oncogenic risk.