Mesenchymal stromal cells equipped by IFNα empower T cells with potent anti-tumor immunity.

Cancer treatments have been revolutionized by the emergence of immune checkpoint blockade therapies. However, only a minority of patients with various tumor types have benefited from such treatments. New strategies focusing on the immune contexture of the tumor tissue microenvironment hold great promises. Here, we created IFNα-overexpressing mesenchymal stromal cells (IFNα-MSCs). Upon direct injection into tumors, we found that these cells are powerful in eliminating several types of tumors. Interestingly, the intra-tumoral injection of IFNα-MSCs could also induce specific anti-tumor effects on distant tumors. These IFNα-MSCs promoted tumor cells to produce CXCL10, which in turn potentiates the infiltration of CD8+ T cells in the tumor site. Furthermore, IFNα-MSCs enhanced the expression of granzyme B (GZMB) in CD8+ T cells and invigorated their cytotoxicity in a Stat3-dependent manner. Genetic ablation of Stat3 in CD8+ T cells impaired the effect of IFNα-MSCs on GZMB expression. Importantly, the combination of IFNα-MSCs and PD-L1 blockade induced an even stronger anti-tumor immunity. Therefore, IFNα-MSCs represent a novel tumor immunotherapy strategy, especially when combined with PD-L1 blockade.