OX40 signaling in head and neck squamous cell carcinoma: Overcoming immunosuppression in the tumor microenvironment

R Bryan Bell; Rom S Leidner; Marka R Crittenden; Brendan D Curti; Zipei Feng; Ryan Montler; Michael J Gough; Bernard A Fox; Andrew D Weinberg; Walter J Urba

doi:10.1016/j.oraloncology.2015.11.009

OX40 signaling in head and neck squamous cell carcinoma: Overcoming immunosuppression in the tumor microenvironment

Oral Oncol. 2016 Jan:52:1-10. doi: 10.1016/j.oraloncology.2015.11.009. Epub 2015 Nov 21.

Authors

Affiliations

¹ 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.
² 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.
³ 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.
⁴ 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.

PMID: 26614363
DOI: 10.1016/j.oraloncology.2015.11.009

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.

Keywords: CTLA-4; Head and neck cancer; Immunotherapy; OX40; Oral cancer; PD-1.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
CTLA-4 Antigen / metabolism
Carcinoma, Squamous Cell / immunology*
Carcinoma, Squamous Cell / metabolism
Head and Neck Neoplasms / immunology*
Head and Neck Neoplasms / metabolism
Humans
Mice
Programmed Cell Death 1 Receptor / metabolism
Receptors, OX40 / immunology*
Receptors, OX40 / metabolism
T-Lymphocytes / immunology*
T-Lymphocytes / metabolism
Tumor Microenvironment

Substances

CTLA-4 Antigen
PDCD1 protein, human
Programmed Cell Death 1 Receptor
Receptors, OX40
TNFRSF4 protein, human