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Discovery of a good responder subtype of esophageal squamous cell carcinoma with cytotoxic T-lymphocyte signatures activated by chemoradiotherapyDiscovery of a good responder subtype of esophageal squamous cell carcinoma with cytotoxic T-lymphocyte signatures activated by chemoradiotherapy |
"/Tanaka, Yosuke/"Tanaka, Yosuke ,
"/Aoyagi, Kazuhiko/"Aoyagi, Kazuhiko ,
"/Minashi, Keiko/"Minashi, Keiko ,
"/Komatsuzaki, Rie/"Komatsuzaki, Rie ,
"/Komatsu, Masayuki/"Komatsu, Masayuki ,
"/Chiwaki, Fumiko/"Chiwaki, Fumiko ,
"/Tamaoki, Masashi/"Tamaoki, Masashi ,
"/Nishimura, Takao/"Nishimura, Takao ,
"/Takahashi, Naoki/"Takahashi, Naoki ,
"/Oda, Ichiro/"Oda, Ichiro ,
"/Tachimori, Yuji/"Tachimori, Yuji ,
"/Arao, Tokuzo/"Arao, Tokuzo ,
"/Nishio, Kazuto/"Nishio, Kazuto ,
"/Kitano, Shigehisa/"Kitano, Shigehisa ,
"/Narumi, Kenta/"Narumi, Kenta ,
"/Aoki, Kazunori/"Aoki, Kazunori ,
"/Fujii, Satoshi/"Fujii, Satoshi ,
"/Ochiai, Atsushi/"Ochiai, Atsushi ,
"/Yoshida, Teruhiko/"Yoshida, Teruhiko ,
"/Muto, Manabu/"Muto, Manabu ,
"/Yamada, Yasuhide/"Yamada, Yasuhide ,
"/Sasaki, Hiroki/"Sasaki, Hiroki
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2015-12-01 , Public Library of Science
ISSN:1932-6203
Description
Definitive chemoradiotherapy (CRT) is a less invasive therapy for esophageal squamous cell carcinoma (ESCC). Five-year survival rate of locally advanced ESCC patients by definitive CRT were 37%. We previously reported that tumor-specific cytotoxic T-lymphocyte (CTL) activation signatures were preferentially found in long-Term survivors. However, it is unknown whether the CTL activation is actually driven by CRT. We compared gene expression profiles among pre-and post-Treatment biopsy specimens of 30 ESCC patients and 121 pre-Treatment ESCC biopsy specimens. In the complete response (CR) cases, 999 overexpressed genes including at least 234 tumor-specific CTL-Activation associated genes such as IFNG, PRF1, and GZMB, were found in post-Treatment biopsy specimens. Clustering analysis using expression profiles of these 234 genes allowed us to distinguish the immune-Activated cases, designating them as I-Type, from other cases. However, despite the better CR rate in the I-Type, overall survival was not significantly better in both these 30 cases and another 121 cases. Further comparative study identified a series of epithelial to mesenchymal transition-related genes overexpressed in the early relapse cases. Importantly, the clinical outcome of CDH2-negative cases in the I-Type was significantly better than that of the CDH2-positive cases in the I-Type. Furthermore, NK cells, which were activated by neutrophils-producing S100A8/S100A9, and CTLs were suggested tocooperatively enhance the effect of CRT in the CDH2-negative I-Type. These results suggested that CTL gene activation may provide a prognostic advantage in ESCCs with epithelial characteristics.
Full-Text
http://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/215108/1/journal.pone.0143804.pdf
