Tada Noriko, Kawai Kazushige, Tsuno Nelson H, Ishihara Soichiro, Yamaguchi Hironori, Sunami Eiji, Kitayama Joji, Oba Koji, Watanabe Toshiaki
Department of Surgical Oncology, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Department of Transfusion Medicine, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
World J Surg Oncol. 2015 Feb 7;13:30. doi: 10.1186/s12957-014-0418-0.
Although neoadjuvant chemoradiotherapy (CRT) has become a standard procedure to downstage locally advanced rectal cancer prior to surgery, markers to predict the response to CRT have not been fully identified. The aim of this study was to identify predictive factors of response to CRT, especially focusing on peripheral blood leukocyte subsets.
A total of 45 consecutive patients diagnosed with primary rectal cancer were prospectively enrolled and received CRT followed by curative resection. The numbers of each lymphocyte subset in peripheral blood pre- and post-CRT were analyzed using flow cytometry. According to the pathological response to CRT, patients were classified into high (Hi-R) and low (Lo-R) response groups.
Hi-R cases had significantly higher numbers of pre-CRT lymphocytes (p = 0.018), T lymphocytes (p = 0.009) and helper T lymphocytes (Th lymphocytes, p = 0.015) compared to the Lo-R cases. With the receiver-operating characteristic curve for numbers of pre-CRT T lymphocytes, the area under the curve (AUC) was 0.733, and the optimal cutoff value was 1196/μl, with 76.5% sensitivity, 67.8% specificity, 59.1% positive and 82.6% negative predictive values. The numbers of pre-CRT Th lymphocytes and cytotoxic lymphocytes were both independent predictors of the high CRT response in the multivariate analysis.
In addition to the direct cytotoxicity of CRT, recent studies have demonstrated the induction of an immunological host response, which also contributed to the tumor regression induced by CRT. Our result suggested the potential role of circulating T lymphocytes in predicting the response to CRT in colorectal cancer patients.
尽管新辅助放化疗（CRT）已成为术前降低局部晚期直肠癌分期的标准治疗方法，但预测CRT疗效的标志物尚未完全明确。本研究旨在确定CRT疗效的预测因素，尤其关注外周血白细胞亚群。
前瞻性纳入45例连续诊断为原发性直肠癌的患者，接受CRT后行根治性切除术。采用流式细胞术分析CRT前后外周血中各淋巴细胞亚群的数量。根据对CRT的病理反应，将患者分为高反应（Hi-R）组和低反应（Lo-R）组。
与Lo-R组相比，Hi-R组CRT前淋巴细胞（p = 0.018）、T淋巴细胞（p = 0.009）和辅助性T淋巴细胞（Th淋巴细胞，p = 0.015）的数量显著更高。根据CRT前T淋巴细胞数量的受试者工作特征曲线，曲线下面积（AUC）为0.733，最佳截断值为1196/μl，敏感性为76.5%，特异性为67.8%，阳性预测值为59.1%，阴性预测值为82.6%。在多变量分析中，CRT前Th淋巴细胞和细胞毒性淋巴细胞的数量均为高CRT反应的独立预测因素。
除了CRT的直接细胞毒性外，最近的研究表明其可诱导宿主免疫反应，这也有助于CRT诱导的肿瘤消退。我们的结果提示循环T淋巴细胞在预测结直肠癌患者对CRT的反应中具有潜在作用。
