title: Triggering of TNFRSF25 promotes CD8⁺ T-cell responses and anti-tumor immunity.
abstract: TNFRSF25 is a member of the TNF receptor superfamily (TNFRSF) that binds to the TNF-like protein TL1A. Although recent studies have demonstrated a role for TNFRSF25 in regulating CD4(+)  T-cell responses, it remains to be determined if TNFRSF25 functions as a costimulatory receptor for CD8(+)  T cells. Here, we demonstrate that ectopic expression of TL1A on mouse plasmacytomas promotes elimination of tumor cells in a CD8(+)  T-cell-dependent manner and renders mice immune to a subsequent challenge with tumor cells. To gain further insight into the role of TNFRSF25 in CD8(+)  T-cell responses, we analyzed the effect of TNFRSF25 triggering on OT-I TCR transgenic T cells. We demonstrate that TNFRSF25 triggering in vivo with soluble TL1A promotes the proliferation and accumulation of antigen-specific CD8(+)  T cells as well as their differentiation into CTLs. Furthermore, we show that TNFRSF25 also functions as a costimulatory receptor for memory CD8(+)  T cells. Thus, TNFRSF25 triggering enhances the secondary expansion of endogenous antigen-specific memory CD8(+)  T cells. Our data suggest that TNFRSF25 agonists, such as soluble TL1A, could potentially be used to enhance the immunogenicity of vaccines that aim to elicit human anti-tumor CD8(+)  T cells.
authors.affiliation: Cancer Sciences Division, University of Southampton School of Medicine, Southampton General Hospital, Southampton, United Kingdom.
authors.forename: Tomasz J
authors.initials: TJ
authors.lastname: Slebioda
authors.forename: Tania F
authors.initials: TF
authors.lastname: Rowley
authors.forename: John R
authors.initials: JR
authors.lastname: Ferdinand
authors.forename: Jane E
authors.initials: JE
authors.lastname: Willoughby
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Buchan
authors.forename: Vadim Y
authors.initials: VY
authors.lastname: Taraban
authors.forename: Aymen
authors.initials: A
authors.lastname: Al-Shamkhani
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010954:Plasmacytoma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D053219:Receptors, Tumor Necrosis Factor, Member 25 / Q000276:immunology / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D053219:Receptors, Tumor Necrosis Factor, Member 25; C506034:Tnfrsf25 protein, mouse; C505947:Tnfsf15 protein, mouse; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15