Mesenchymal stromal cells 2.0: thinking outside the box

Mesenchymal stromal cells (MSCs) are non-hematopoietic progenitor cells that can be derived from a variety of sources including bone marrow and adipose tissues among others. MSCs are plastic adherent and easy to culture ex vivo, making them attractive platforms for cell-based technologies. They have an impressive immunoplasticity and can express a suppressive or inflammatory phenotype depending on their stimuli. While MSCs are mainly used in tissue regeneration or as a tool to suppress unwanted inflammation, their pro-inflammatory phenotype includes their ability to act as antigen presenting cells (APCs). This property, along with their ease of expansion and manipulation, make them excellent candidates as alternatives to dendritic cell-based technologies, especially for cancer vaccination. To generate stable MSCs with an APC-like phenotype, two main venues have been explored: genetic and pharmacological reprogramming. Routes to generating MSC-APCs have shown great promise in therapeutic and prophylactic settings in vivo, demonstrating effective tumor control in multiple murine models. Mechanistically, MSC-APCs appear to be generated in response to reactive oxygen species and endoplasmic reticulum stress. While much remains to be uncovered with respect to their phenotype, these reprogrammed cells show great promise as the next generation of cancer vaccine platforms. Herein, we describe the state-of-the-art in routes to reprogramming MSCs and discuss their future in the immune-oncology space as potent cancer vaccines.