Light Modified Mesenchymal Stem Cells Prime Anti-tumor Immunity

How to effectively target tumor tissues with immune stimulatory molecules and reverse suppressive tumor environment has been challenging. Mesenchymal stem cells (MSCs) may home to tumor tissues and incorporate as cancer associated fibroblasts (CAFs) to promote tumor growth. Based on the findings that the tumor-necrosis factor superfamily14(LIGHT) within tumor tissues can organize potent immunity against tumor, herein we tested whether MSCs engineered to expression of LIGHT (MSC-L) could deliver LIGHT to tumor tissues and break immune tolerance by changing tumor micro-environments. With in vitro and in vivo migration assays, we found that MSC-L possessed strong iropism to tumor tissues. Impressively, we also showed that MSC-L could induce host immune cell lysing MSCs and CAFs. With either the prophylactic or therapeutic animal protocol, we observed that MSC-L could orchestrate with tumor vaccine to reject tumor by organizing immunity against tumor cells and CAFs via LIGHT signaling. Furthermore, we revealed that CD4T cells played a role in the induction phase, while CD8T was essential for effector phase. Thus, our results indicate that properly modulated MSC can reverse tumor suppressive environment by promoting immunity against tumor cell and CAFs and would largely facilitate tumor vaccine to reject tumor.