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Ki67 expression and localization of T cells after neoadjuvant therapies as reliable predictive markers in rectal cancer

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Title: Ki67 expression and localization of T cells after neoadjuvant therapies as reliable predictive markers in rectal cancer
Authors: Imaizumi, Ken Browse this author
Suzuki, Toshihiro Browse this author
Kojima, Motohiro Browse this author →KAKEN DB
Shimomura, Manami Browse this author
Sakuyama, Naoki Browse this author
Tsukada, Yuichiro Browse this author
Sasaki, Takeshi Browse this author
Nishizawa, Yuji Browse this author →KAKEN DB
Taketomi, Akinobu Browse this author →KAKEN DB
Ito, Masaaki Browse this author →KAKEN DB
Nakatsura, Tetsuya Browse this author →KAKEN DB
Keywords: multiplexed fluorescent immunohistochemistry
neoadjuvant chemoradiotherapy
neoadjuvant chemotherapy
rectal cancer
tumor-infiltrating lymphocyte
Issue Date: Jan-2020
Publisher: John Wiley & Sons
Journal Title: Cancer science
Volume: 111
Issue: 1
Start Page: 23
End Page: 35
Publisher DOI: 10.1111/cas.14223
Abstract: Chemoradiotherapy (CRT) is the standard neoadjuvant therapy for locally advanced rectal cancer (RC). However, neoadjuvant chemotherapy (NAC) also shows favorable outcomes. Although the immunological environment of RC has been thoroughly discussed, the effect of NAC on it is less clear. Here, we investigated the immunological microenvironment, including T cell infiltration, activation, and topological distribution, of resected RC tissue after neoadjuvant therapies and evaluated the correlation between T cell subsets and patient prognosis. Rectal cancer patients (n = 188) were enrolled and categorized into 3 groups, namely CRT (n = 41), NAC (n = 46), and control (surgery alone; n = 101) groups. Characterization of residual carcinoma cells and T cell subsets in resected tissues was performed using multiplex fluorescence immunohistochemistry. The densities of total and activated (Ki67(high)) T cells in tissues after NAC, but not CRT, were higher than in control. In both CRT and NAC groups, patients presenting with higher treatment effects showed aggressive infiltration of T cell subsets into carcinomas. Multivariate analyses of pathological and immunological features and prognosis revealed that carcinoma Ki67(high)CD4(+) T cells after CRT and stromal Ki67(high)CD8(+) T cells after NAC are important prognostic factors, respectively. Our results suggest that evaluation of T cell activation with Ki67 expression and its tumor localization can be used to determine the prognosis of advanced RC after neoadjuvant therapies.
Type: article
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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