Abstract
Abstract Introduction Foxp3+ regulatory T cells (Tregs) have been thought to have at least two subsets: natural Tregs (nTregs) and induced Tregs (iTregs). Recently, expression of the transcription factor Helios, a member of the Ikaros gene family, has been expected to be a molecular marker of nTregs, but this is still controversial. To date, several in vitro studies and animal model studies regarding Helios have been reported, but there has been no examination of the clinical impact of Helios expression on Tregs in patients with lung cancer to date. Methods A total of 45 non-small cell lung cancer (NSCLC) patients who underwent surgical resection and 19 advanced/recurrent NSCLC patients was evaluated. Peripheral blood mononuclear cells (PBMCs) taken from these patients were examined by flow-cytometry. Of these 45 patients, 18 who were evaluable for tumor tissue underwent immunohistochemical investigation for tumor-infiltrating lymphocytes. Results Helios-negative Tregs of CD4+ T cells were significantly higher not only in all cancer patients (2.4%), but also in stage IA patients (2.6%) as compared with normal controls (1.5%, p<0.001). Patients who had a lower level of Helios-negative Tregs in tumor-infiltrating lymphocytes had significantly longer survival (p = 0.038). Discussion Helios-negative Tregs may be involved in immune suppression, even in early-stage NSCLC. The frequency of Helios-negative Tregs could be a useful prognostic biomarker in patients with NSCLC. The biological functions of Helios-negative Tregs in immune suppression should be further examined. Baseline demographicsCharacteristicN (%)Age (y)Mean±SD67±8SexFemale27 (42)Male37 (58)Pathological stageIA22 (34)IB16 (25)IIA4 (6)IIB3 (5)III0 (0)IV (Recurrence included)Chemotherapy1st-line6 (9)2nd-line6 (9)3rd or later-line7 (11)Pathological classificationAdenocarcinoma51 (80)Squamous cell carcinoma10 (16)Others3 (5)EGFR mutationPositive22 (34)Negative31 (48)Unknown11 (17) Citation Format: 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. Clinical features of transcriptional factor Helios expression on regulatory T cells in patients with non-small cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1280. doi:10.1158/1538-7445.AM2015-1280
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