Mesenchymal stromal cells equipped by IFN alpha 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 IFN alpha-overexpressing mesenchymal stromal cells (IFN alpha-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 IFN alpha-MSCs could also induce specific anti-tumor effects on distant tumors. These IFN alpha-MSCs promoted tumor cells to produce CXCL10, which in turn potentiates the infiltration of CD8(+) T cells in the tumor site. Furthermore, IFN alpha-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 IFN alpha-MSCs on GZMB expression. Importantly, the combination of IFN alpha-MSCs and PD-L1 blockade induced an even stronger anti-tumor immunity. Therefore, IFN alpha-MSCs represent a novel tumor immunotherapy strategy, especially when combined with PD-L1 blockade.

Automated summary

The emergence of immune checkpoint blockade therapies has revolutionized cancer treatments. However, only a minority of patients have benefited from these treatments. New strategies focusing on the immune contexture of the tumor tissue microenvironment show great promise. IFN alpha-MSCs, when injected directly into tumors, have shown to be powerful in eliminating various tumor types and inducing anti-tumor effects on distant tumors. This is achieved by promoting the production of CXCL10 and enhancing the infiltration and cytotoxicity of CD8(+) T cells.