title: Clinical significance of expanded Foxp3⁺ Helios⁻ regulatory T cells in patients with non-small cell lung cancer.
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.
authors.affiliation: Department of Regenerative Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Muto
authors.affiliation: Department of Regenerative Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Owada
authors.affiliation: Department of Regenerative Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Regenerative Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Regenerative Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Yamaura
authors.affiliation: Department of Regenerative Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Mitsuro
authors.initials: M
authors.lastname: Fukuhara
authors.affiliation: Department of Regenerative Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Okabe
authors.affiliation: Department of Regenerative Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsumura
authors.affiliation: Department of Regenerative Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Department of Regenerative Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Osugi
authors.affiliation: Department of Regenerative Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Hoshino
authors.affiliation: Department of Regenerative Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Higuchi
authors.affiliation: Department of Regenerative Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Regenerative Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Mitsukazu
authors.initials: M
authors.lastname: Gotoh
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D051740:Ikaros Transcription Factor / Q000096:biosynthesis / Q000276:immunology; D007150:Immunohistochemistry; D016130:Immunophenotyping; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C111431:IKZF2 protein, human; D051740:Ikaros Transcription Factor