Matsutani Shinji, Shibutani Masatsune, Maeda Kiyoshi, Nagahara Hisashi, Fukuoka Tatsunari, Nakao Shigetomi, Hirakawa Kosei, Ohira Masaichi
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Cancer Sci. 2018 Apr;109(4):966-979. doi: 10.1111/cas.13542. Epub 2018 Mar 25.
Neoadjuvant therapy for locally advanced rectal cancer is becoming increasingly common. However, biomarkers predicting the response to neoadjuvant therapy have not been established. Tumor-infiltrating lymphocytes (TILs) have a crucial effect on tumor progression and survival outcome as the primary host immune response, and an antitumor immune effect has been reported to contribute to the response to radiotherapy and chemotherapy. We investigated the significance of TILs before and after neoadjuvant treatment and the change in the density of those TILs. Sixty-four patients who underwent radical resection after neoadjuvant treatment for locally advanced rectal cancer were enrolled. The number of TIL subsets was examined using immunohistochemical staining of pretreatment biopsy samples and post-treatment resected specimens. In both the neoadjuvant chemotherapy cohort and the neoadjuvant chemoradiotherapy cohort, a low density of CD8 TILs in pretreatment biopsy samples was associated with a poor response, and a low density of CD8 TILs in post-treatment resected specimens was similarly associated with a poor response. In the neoadjuvant chemoradiotherapy cohort, the density of CD8 TILs in post-treatment resected specimens was significantly increased compared with that in pretreatment biopsy samples. We concluded that T lymphocyte-mediated immune reactions play an important role in tumor response to neoadjuvant treatment for rectal cancer, and the evaluation of TILs in pretreatment biopsy samples might be a predictor of the clinical effectiveness of neoadjuvant treatment. Furthermore, neoadjuvant therapy, especially chemoradiotherapy, could induce the activation of the local immune status.
局部晚期直肠癌的新辅助治疗正变得越来越普遍。然而，预测新辅助治疗反应的生物标志物尚未确立。肿瘤浸润淋巴细胞（TILs）作为主要的宿主免疫反应，对肿瘤进展和生存结果具有关键作用，并且据报道抗肿瘤免疫效应有助于对放疗和化疗的反应。我们研究了新辅助治疗前后TILs的意义以及这些TILs密度的变化。纳入了64例接受局部晚期直肠癌新辅助治疗后行根治性切除术的患者。使用预处理活检样本和治疗后切除标本的免疫组织化学染色来检查TIL亚群的数量。在新辅助化疗队列和新辅助放化疗队列中，预处理活检样本中CD8 TILs的低密度与反应不佳相关，治疗后切除标本中CD8 TILs的低密度同样与反应不佳相关。在新辅助放化疗队列中，治疗后切除标本中CD8 TILs的密度与预处理活检样本相比显著增加。我们得出结论，T淋巴细胞介导的免疫反应在直肠癌对新辅助治疗的反应中起重要作用，并且预处理活检样本中TILs的评估可能是新辅助治疗临床疗效的一个预测指标。此外，新辅助治疗，尤其是放化疗，可诱导局部免疫状态的激活。
