title: OX40 signaling in head and neck squamous cell carcinoma: Overcoming immunosuppression in the tumor microenvironment.
abstract: OX40 is a member of the tumor necrosis factor (TNF) receptor family and a potent co-stimulatory pathway that when triggered can enhance T-cell memory, proliferation and anti-tumor activity in patients with metastatic cancer. Ongoing investigations at our institution have demonstrated that OX40 expressing T cells are found in abundance in the tumors of patients with advanced stage head and neck squamous cell carcinoma (HNSCC). This has led to the initiation of human clinical trials investigating OX40-directed therapy for patients with HNSCC in both the metastatic and curative setting. The purpose of this review is to explore what is known about OX40 signaling and discuss how this pathway potentially can be modulated to improve outcome for patients with HNSCC.
authors.affiliation: Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at the Providence Cancer Center, 4805 NE Glisan St. Suite 2N35, Portland, OR 97213, United States; Providence Oral, Head and Neck Cancer Program and Clinic, Providence Cancer Center, Providence Portland Medical Center, 4805 NE Glisan St. Suite 6N50, Portland, OR 97213, United States; Oregon Health and Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, United States; Head and Neck Institute, 1849 NW Kearney, Suite 300, Portland, OR 97209, United States. Electronic address: richard.bell@providence.org.
authors.forename: R Bryan
authors.initials: RB
authors.lastname: Bell
authors.affiliation: Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at the Providence Cancer Center, 4805 NE Glisan St. Suite 2N35, Portland, OR 97213, United States; Providence Oral, Head and Neck Cancer Program and Clinic, Providence Cancer Center, Providence Portland Medical Center, 4805 NE Glisan St. Suite 6N50, Portland, OR 97213, United States.
authors.forename: Rom S
authors.initials: RS
authors.lastname: Leidner
authors.affiliation: Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at the Providence Cancer Center, 4805 NE Glisan St. Suite 2N35, Portland, OR 97213, United States; Providence Oral, Head and Neck Cancer Program and Clinic, Providence Cancer Center, Providence Portland Medical Center, 4805 NE Glisan St. Suite 6N50, Portland, OR 97213, United States.
authors.forename: Marka R
authors.initials: MR
authors.lastname: Crittenden
authors.affiliation: Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at the Providence Cancer Center, 4805 NE Glisan St. Suite 2N35, Portland, OR 97213, United States.
authors.forename: Brendan D
authors.initials: BD
authors.lastname: Curti
authors.affiliation: Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at the Providence Cancer Center, 4805 NE Glisan St. Suite 2N35, Portland, OR 97213, United States; Oregon Health and Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, United States.
authors.forename: Zipei
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at the Providence Cancer Center, 4805 NE Glisan St. Suite 2N35, Portland, OR 97213, United States; Oregon Health and Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, United States.
authors.forename: Ryan
authors.initials: R
authors.lastname: Montler
authors.affiliation: Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at the Providence Cancer Center, 4805 NE Glisan St. Suite 2N35, Portland, OR 97213, United States.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Gough
authors.affiliation: Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at the Providence Cancer Center, 4805 NE Glisan St. Suite 2N35, Portland, OR 97213, United States; Oregon Health and Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, United States.
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Fox
authors.affiliation: Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at the Providence Cancer Center, 4805 NE Glisan St. Suite 2N35, Portland, OR 97213, United States; Oregon Health and Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, United States.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Weinberg
authors.affiliation: Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at the Providence Cancer Center, 4805 NE Glisan St. Suite 2N35, Portland, OR 97213, United States.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Urba
mesh_terms: D000818:Animals; D060908:CTLA-4 Antigen / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D053262:Receptors, OX40 / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: D060908:CTLA-4 Antigen; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D053262:Receptors, OX40; C505716:TNFRSF4 protein, human
keywords: CTLA-4; Head and neck cancer; Immunotherapy; OX40; Oral cancer; PD-1