title: Signaling through OX40 enhances antitumor immunity.
abstract: The existence of tumor-specific T cells, as well as their ability to be primed in cancer patients, confirms that the immune response can be deployed to combat cancer. However, there are obstacles that must be overcome to convert the ineffective immune response commonly found in the tumor environment to one that leads to sustained destruction of tumor. Members of the tumor necrosis factor (TNF) superfamily direct diverse immune functions. OX40 and its ligand, OX40L, are key TNF members that augment T-cell expansion, cytokine production, and survival. OX40 signaling also controls regulatory T-cell differentiation and suppressive function. Studies over the past decade have demonstrated that OX40 agonists enhance antitumor immunity in preclinical models using immunogenic tumors; however, treatment of poorly immunogenic tumors has been less successful. Combining strategies that prime tumor-specific T cells together with OX40 signaling could generate and maintain a therapeutic antitumor immune response.
authors.affiliation: Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Cancer Center, Providence Portland Medical Center, Portland, OR 97213, USA. shawn.jensen@providence.org
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Jensen
authors.forename: Levi D
authors.initials: LD
authors.lastname: Maston
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Gough
authors.forename: Carl E
authors.initials: CE
authors.lastname: Ruby
authors.forename: William L
authors.initials: WL
authors.lastname: Redmond
authors.forename: Marka
authors.initials: M
authors.lastname: Crittenden
authors.forename: Yuhuan
authors.initials: Y
authors.lastname: Li
authors.forename: Sachin
authors.initials: S
authors.lastname: Puri
authors.forename: Christian H
authors.initials: CH
authors.lastname: Poehlein
authors.forename: Nick
authors.initials: N
authors.lastname: Morris
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kovacsovics-Bankowski
authors.forename: Tarsem
authors.initials: T
authors.lastname: Moudgil
authors.forename: Chris
authors.initials: C
authors.lastname: Twitty
authors.forename: Edwin B
authors.initials: EB
authors.lastname: Walker
authors.forename: Hong-Ming
authors.initials: HM
authors.lastname: Hu
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Urba
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Weinberg
authors.forename: Brendan
authors.initials: B
authors.lastname: Curti
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Fox
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D019496:Cancer Vaccines; D003131:Combined Modality Therapy; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016219:Immunotherapy, Adoptive; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D053278:OX40 Ligand / Q000819:agonists / Q000276:immunology*; D053262:Receptors, OX40 / Q000819:agonists / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D053278:OX40 Ligand; D053262:Receptors, OX40; C505716:TNFRSF4 protein, human