title: LIGHT delivery to tumors by mesenchymal stem cells mobilizes an effective antitumor immune response.
abstract: Bone marrow-derived mesenchymal stem cells (MSC) have been shown to home into tumor tissues, where they promote tumor growth and suppress immune rejection. In this study, we tested whether MSCs engineered to express the immune stimulating factor LIGHT, a member of the TNF superfamily, could induce tumor regression. Using in vitro and in vivo migration assays, we found that LIGHT-expressing MSCs (MSC-L) displayed a strong tropism for tumor tissues. MSC-L treatment activated the LIGHT-signaling pathway, effectively organizing a potent antitumor immune response that stimulated an influx of T cells and inhibited tumor growth in vivo. CD4 T cells were found to play a role in the induction phase of the immune response, and CD8 T cells were shown to be essential for the effector phase. Together, our findings indicate that MSCs can effectively home into and deliver immune stimulating molecules to tumor tissues, thereby reversing the immune-suppressive environment, promoting antitumor immunity, and inhibiting tumor growth.
authors.affiliation: Program of Innovative Cancer Therapeutics, The First affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Weibin
authors.initials: W
authors.lastname: Zou
authors.forename: Huilin
authors.initials: H
authors.lastname: Zheng
authors.forename: Tong-Chuan
authors.initials: TC
authors.lastname: He
authors.forename: Jinjia
authors.initials: J
authors.lastname: Chang
authors.forename: Yang-Xin
authors.initials: YX
authors.lastname: Fu
authors.forename: Weimin
authors.initials: W
authors.lastname: Fan
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D015398:Signal Transduction; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000378:metabolism*
chemical_list: C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D007371:Interferon-gamma