Concerted immune evasion and intrinsic inflammation as consequence of in vitro neoplastic transformation of mesenchymal stem cells

Immune escape is one of the essential properties of tumors. However, there are no evidences discriminating if the establishment of the immune suppressor phenotype is exclusively determined by the immune system pressure on tumor progression, or intrinsically supported by the events leading to neoplastic transformation. To unravel this dichotomy, we used two in vitro models based on the sequential transformation of mesenchymal stem cells (MSC). Malignant transformation reinforces the natural immune escape properties of MSC, mediated by the reduction of membrane HLA class I levels and the increasing inhibitory capacity on T cells. It was evidenced that as a consequence of transformation, there is a transition in the natural inhibitory effect of MSC on T-cell proliferation from an inducible mechanism depending on IFN-γ signaling and mediated by indoleamine 2,3-dioxygenase towards a constitutive mechanism involving TGF-β, HGF, COX-2 and PDL-1. It was found that the increased expression of the inflammatory mediators IL-1β and PGE₂ caused by the neoplastic transformation of MSC supports the immune suppressor properties of these cells. Our results indicate that oncogenic signals are able to concert intrinsic inflammation and immune escape, independently of the selective pressure of the immune system. This research granted the 2015 Award of the Cuban National Academy of Sciences.