title: Myeloid-derived suppressor cells promote age-related increase of lung cancer growth via B7-H1.
abstract: Accumulation of myeloid-derived suppressor cells (MDSCs) in aged hosts contribute to the age-related increase of susceptibility to murine breast adenocarcinoma and co-stimulatory molecules expressed in MDSCs are essential for MDSCs-mediated immune suppression. However, the co-stimulatory molecules that exert a direct effect on MDSCs-mediated age-dependent tumor susceptibility and the regulatory mechanism of their expression remain unclear. In the present study, we found that accumulation of MDSCs in aged mice was closely correlated with age-dependent enhanced growth of lung cancer. Further analysis revealed that B7-H1 was highly expressed in the MDSCs of 18-month but not in 2-month old mice. Accordingly, inhibition of B7-H1 with B7-H1 specific antibody significantly reactivated T cells and reduced the tumor progression mediated by MDSCs. In addition, IL-10 released from 18-month old mice stimulated the expression of B7-H1 on MDSCs. These results suggest that B7-H1 expressed on MDSCs is a novel target for reducing lung cancer susceptibility as the age increases.
authors.affiliation: Special Procurement Ward, First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.
authors.forename: Siwen
authors.initials: S
authors.lastname: Chen
authors.affiliation: Special Procurement Ward, First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Liu
authors.affiliation: Respiratory Intensive Care Unit, Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Su
authors.affiliation: Clinical Immunology Laboratory, First Affiliated Hospital, Suzhou 215006, Jiangsu Province, China.
authors.forename: Guangbo
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Special Procurement Ward, First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China. Electronic address: wangling40@126.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
mesh_terms: D000367:Age Factors; D000818:Animals; D060890:B7-H1 Antigen / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004198:Disease Susceptibility; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000502:physiology; D008175:Lung Neoplasms / Q000209:etiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; C556062:IL10 protein, mouse; D016753:Interleukin-10
keywords: Aging; B7-H1; Immune suppression; Lung cancer; Myeloid-derived suppressor cells