title: CD40 controls CXCR5-induced recruitment of myeloid-derived suppressor cells to gastric cancer.
abstract: To explore the mechanisms of MDSC trafficking and accumulation during tumor progression. In this study, we report significant CD40 upregulation in tumor-infiltrating MDSC when compared with splenic MDSC. Microarray analyses comparing CD40(high) and CD40l(ow) MDSC revealed 1872 differentially expressed genes, including CD83, CXCR5, BTLA, CXCL9, TLR1, FLT3, NOD2 and CXCL10. In vivo experiments comparing wild-type (WT) and CD40 knockout (KO) mice demonstrated that CD40 critically regulates CXCR5 expression. Consistently, the transwell analysis confirmed the essential role of CXCR5-CXCL13 crosstalk in the migration of CD40+ MDSC toward gastric cancer. Furthermore, more MDSC accumulated in the gastric cancers of WT mice when compared with KO mice, and the WT tumors mostly contained CD40+ cells. Functionally, tumors grew faster in WT than KO mice. In conclusion, we demonstrate that CD40 expression upregulates the chemokine receptor CXCR5 and promotes MDSC migration toward and accumulation within cancer. Therefore, this study provides preliminary evidence that CD40 may stimulate tumor growth by enabling immune evasion via MDSC recruitment and inhibition of T cell expansion.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Shen
authors.affiliation: Key Laboratory of Medicine and Clinical Immunology of Jiangsu Province, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Guangbo
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: JiaMing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.|Key Laboratory of Medicine and Clinical Immunology of Jiangsu Province, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Weichang
authors.initials: W
authors.lastname: Chen
mesh_terms: D000818:Animals; D019013:CD40 Antigens / Q000276:immunology*; D049109:Cell Proliferation / Q000502:physiology; D020869:Gene Expression Profiling; D064593:Heterografts; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology* / Q000473:pathology; D054380:Receptors, CXCR5 / Q000235:genetics / Q000276:immunology*; D013274:Stomach Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D019013:CD40 Antigens; C095085:CXCR5 protein, human; D054380:Receptors, CXCR5
keywords: CD40; CXCR5; gastric cancer; immune evasion; myeloid-derived suppressor cells