title: CD27 signaling increases the frequency of regulatory T cells and promotes tumor growth.
abstract: Signaling of the TNF receptor superfamily member CD27 activates costimulatory pathways to elicit T- and B-cell responses. CD27 signaling is regulated by the expression of its ligand CD70 on subsets of dendritic cells and lymphocytes. Here, we analyzed the role of the CD27-CD70 interaction in the immunologic control of solid tumors in Cd27-deficient mice. In tumor-bearing wild-type mice, the CD27-CD70 interaction increased the frequency of regulatory T cells (Tregs), reduced tumor-specific T-cell responses, increased angiogenesis, and promoted tumor growth. CD27 signaling reduced apoptosis of Tregs in vivo and induced CD4(+) effector T cells (Teffs) to produce interleukin-2, a key survival factor for Tregs. Consequently, the frequency of Tregs and growth of solid tumors were reduced in Cd27-deficient mice or in wild-type mice treated with monoclonal antibody to block CD27 signaling. Our findings, therefore, provide a novel mechanism by which the adaptive immune system enhances tumor growth and may offer an attractive strategy to treat solid tumors.
authors.affiliation: Tumor Immunology, Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Christina
authors.initials: C
authors.lastname: Claus
authors.forename: Carsten
authors.initials: C
authors.lastname: Riether
authors.forename: Christian
authors.initials: C
authors.lastname: Schürch
authors.forename: Matthias S
authors.initials: MS
authors.lastname: Matter
authors.forename: Tamara
authors.initials: T
authors.lastname: Hilmenyuk
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Ochsenbein
mesh_terms: D000818:Animals; D053282:CD27 Ligand / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*
chemical_list: D053282:CD27 Ligand; D007376:Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7