Open AccessOX40, PD‐1 and CTLA‐4 are selectively expressed on tumor‐infiltrating T cells in head and neck cancer
Author(s) -
Montler Ryan,
Bell R Bryan,
Thalhofer Colin,
Leidner Rom,
Feng Zipei,
Fox Bernard A,
Cheng Allen C,
Bui Tuan G,
Tucker Christopher,
Hoen Helena,
Weinberg Andrew
Publication year - 2016
Publication title -
clinical and translational immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.321
H-Index - 34
ISSN - 2050-0068
DOI - 10.1038/cti.2016.16
Subject(s) - cd8 , tumor infiltrating lymphocytes , cytotoxic t cell , ctla 4 , immune system , population , t cell , cancer research , head and neck squamous cell carcinoma , immunology , tumor microenvironment , medicine , cancer , biology , head and neck cancer , in vitro , biochemistry , environmental health
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.