title: OX40, PD-1 and CTLA-4 are selectively expressed on tumor-infiltrating T cells in head and neck cancer.
abstract: The tumor microenvironment of squamous cell carcinoma of the head and neck (SCCHN) has been shown to be immune suppressive. Therefore, strategies aimed at overcoming this issue could have a positive therapeutic impact. Hence, we investigated the expression of the known immune-modulatory proteins OX40, programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in SCCHN on different T-cell subsets of tumor-infiltrating lymphocytes (TIL) to ascertain whether these proteins could potentially be targeted alone or in combination for future clinical trials. T cells from peripheral blood (PBL) and tumor were analyzed for the expression of OX40, PD-1 and CTLA-4 in 29 patients undergoing surgery. These proteins were all expressed significantly higher in T-cell subsets isolated from tumors compared with PBL of the same patient. OX40 expression was significantly greater in the TIL regulatory T-cell (Treg) population relative to conventional CD4 and CD8 TIL or the Treg isolated from PBL. PD-1 expression was increased in all T-cell subsets relative to PBL. CTLA-4 was also increased in all TIL subsets relative to blood, and similar to OX40, its highest level of expression was observed in the Treg TIL. The highest frequency of PD-1, CTLA-4 and OX40 triple-positive cells were found in the Treg population isolated from the tumor. We analyzed both human papilloma virus-positive and -negative patients and found similar levels and expression patterns of these two patient populations for all three proteins. These data suggest that there may be therapeutic advantages of targeting these pathways independently or in combination for patients with this disease.
authors.affiliation: AgonOx, Inc. , Portland, OR, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Montler
authors.affiliation: Earle A Chiles Research Institute in the Providence Cancer Center, Portland, OR, USA; Providence Oral, Head and Neck Cancer Program and Clinic, Providence Cancer Center, Providence Portland Medical Center, Portland, OR, USA.
authors.forename: R Bryan
authors.initials: RB
authors.lastname: Bell
authors.affiliation: AgonOx, Inc. , Portland, OR, USA.
authors.forename: Colin
authors.initials: C
authors.lastname: Thalhofer
authors.affiliation: Earle A Chiles Research Institute in the Providence Cancer Center, Portland, OR, USA; Providence Oral, Head and Neck Cancer Program and Clinic, Providence Cancer Center, Providence Portland Medical Center, Portland, OR, USA.
authors.forename: Rom
authors.initials: R
authors.lastname: Leidner
authors.affiliation: Earle A Chiles Research Institute in the Providence Cancer Center, Portland, OR, USA; Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Zipei
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Earle A Chiles Research Institute in the Providence Cancer Center , Portland, OR, USA.
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Fox
authors.affiliation: Providence Oral, Head and Neck Cancer Program and Clinic, Providence Cancer Center, Providence Portland Medical Center , Portland, OR, USA.
authors.forename: Allen C
authors.initials: AC
authors.lastname: Cheng
authors.affiliation: Providence Oral, Head and Neck Cancer Program and Clinic, Providence Cancer Center, Providence Portland Medical Center , Portland, OR, USA.
authors.forename: Tuan G
authors.initials: TG
authors.lastname: Bui
authors.affiliation: AgonOx, Inc., Portland, OR, USA; Earle A Chiles Research Institute in the Providence Cancer Center, Portland, OR, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Tucker
authors.affiliation: Earle A Chiles Research Institute in the Providence Cancer Center , Portland, OR, USA.
authors.forename: Helena
authors.initials: H
authors.lastname: Hoen
authors.affiliation: AgonOx, Inc., Portland, OR, USA; Earle A Chiles Research Institute in the Providence Cancer Center, Portland, OR, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Weinberg