Clinical significance of expanded Foxp3+ Helios- regulatory T cells in patients with non-small cell lung cancer

Muto,Satoshi; Owada,Yuki; Inoue,Takuya; Watanabe,Yuzuru; Yamaura,Takumi; Fukuhara,Mitsuro; Okabe,Naoyuki; Matsumura,Yuki; Hasegawa,Takeo; Osugi,Jun; Hoshino,Mika; Higuchi,Mitsunori; Suzuki,Hiroyuki; Gotoh,Mitsukazu

doi:10.3892/ijo.2015.3196

Clinical significance of expanded Foxp3+ Helios- regulatory T cells in patients with non-small cell lung cancer

Authors:
- Satoshi Muto
- Yuki Owada
- Takuya Inoue
- Yuzuru Watanabe
- Takumi Yamaura
- Mitsuro Fukuhara
- Naoyuki Okabe
- Yuki Matsumura
- Takeo Hasegawa
- Jun Osugi
- Mika Hoshino
- Mitsunori Higuchi
- Hiroyuki Suzuki
- Mitsukazu Gotoh
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Affiliations: Department of Regenerative Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan
Published online on: October 12, 2015 https://doi.org/10.3892/ijo.2015.3196
Pages: 2082-2090
Copyright: © Muto et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The functions of different regulatory T cell (Treg) types in cancer progression are unclear. Recently, expression of the transcription factor Helios was proposed as a marker for natural (non-induced) Tregs. The present study investigated the clinical significance of Helios expression in patients with non-small cell lung cancer (NSCLC). We enrolled 64 patients with NSCLC, of whom 45 were treated surgically and 19 received chemotherapy because of advanced/recurrent disease. Their peripheral blood mononuclear cells were examined by flow cytometry. From the 45 surgery patients, we matched 9 patients with recurrent disease with 9 stage-matched patients without recurrence (n=18), compared their specimens immunohistochemically for tumor infiltrating lymphocytes (TILs) and analyzed these data against clinicopathological factors. Helios expression in Foxp3+ Tregs was 47.5±13.3% in peripheral blood and 18.1±13.4% in tumor specimens. Percentage of Helios- Tregs among CD4+ T cells were significantly higher in the cancer patients (2.4%), especially those with stage IA disease (2.6%) than in healthy donors (1.5%; P<0.001). Patients with low levels of Helios expression in Tregs among their TILs had significantly poorer survival (P=0.038). Helios- Tregs may affect immune suppression, even in early stage NSCLC; they could also be a useful prognostic biomarker in patients with NSCLC, and possibly a novel cancer immunotherapy target.

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