T-cell complexity and density are associated with sensitivity to neoadjuvant chemoradiotherapy in patients with rectal c
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ORIGINAL ARTICLE
T‑cell complexity and density are associated with sensitivity to neoadjuvant chemoradiotherapy in patients with rectal cancer Takashi Akiyoshi1 · Osamu Gotoh2 · Norio Tanaka2 · Kazuma Kiyotani2 · Noriko Yamamoto3 · Masashi Ueno4 · Yosuke Fukunaga1 · Seiichi Mori2 Received: 12 July 2020 / Accepted: 18 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Emerging evidence suggests that an increased density of pre-treatment C D8+ tumor-infiltrating lymphocytes (TILs) is associated with good response to chemoradiotherapy (CRT) in patients with locally advanced rectal cancer. However, the significance of T-cell complexity in the clinical setting remains unknown. High-throughput T-cell receptor (TCR) β sequencing was applied to quantify the TCR repertoire of pre-treatment biopsies from 67 patients with advanced rectal cancer receiving preoperative CRT. Diversity index was used to represent the complexity of the TCR repertoire in a tumor. Pre-treatment CD8+ TIL densities were assessed by immunohistochemistry. Changes in TCR repertoire before and after CRT were also analysed in 23 patients. Diversity indices were significantly higher for good responders than for non-responders (P = 0.031). The multivariate analysis revealed that both C D8+ TIL density and TCR diversity index were independently associated with good response to CRT (P 0.3 was set as a threshold for selecting the terms for clustering. Two-sided P values
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