Significance of tumor-infiltrating lymphocytes before and after neoadjuvant therapy for rectal cancer.
Significance of tumor-infiltrating lymphocytes before and after neoadjuvant therapy for rectal cancer.
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DOI：
10.1111/cas.13542
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发表时间：
2018-04
期刊：
影响因子：
5.7
通讯作者：
Ohira M
中科院分区：
文献类型：
--
作者：
Matsutani S;Shibutani M;Maeda K;Nagahara H;Fukuoka T;Nakao S;Hirakawa K;Ohira M
局部晚期直肠癌的新辅助治疗变得越来越普遍。然而，预测新辅助治疗反应的生物标志物尚未建立。肿瘤浸润淋巴细胞（TIL）作为主要的宿主免疫反应对肿瘤进展和生存结果具有至关重要的影响，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 TIL 的意义以及这些 TIL 密度的变化。纳入 64 例局部晚期直肠癌新辅助治疗后接受根治性切除的患者。使用治疗前活检样本和治疗后切除标本的免疫组织化学染色检查 TIL 子集的数量。在新辅助化疗队列和新辅助放化疗队列中，治疗前活检样本中 CD8+ TIL 密度低与反应不良相关，治疗后切除标本中 CD8+ TIL 密度低同样与反应不良相关。在新辅助放化疗队列中，与治疗前活检样本相比，治疗后切除标本中 CD8+ TIL 的密度显着增加。我们的结论是，T 淋巴细胞介导的免疫反应在直肠癌新辅助治疗的肿瘤反应中发挥重要作用，治疗前活检样本中 TIL 的评估可能是新辅助治疗临床有效性的预测指标。此外，新辅助治疗，尤其是放化疗，可以诱导局部免疫状态的激活。
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.