Louis Pasteur Center for Medical Research, 103-5, Tanakamonzen-cho, Sakyo-ku, Kyoto City, Kyoto, 606-8225, Japan.
Cancer Immunol Immunother. 2010 Oct;59(10):1457-65. doi: 10.1007/s00262-010-0868-3. Epub 2010 Jun 1.
The ability to predict anti-tumor immune responses at local tumor growing sites using only peripheral blood specimens would be helpful in determining therapeutic options for patients with solid tumors. Here, we show that the glutathione intracellular content (icGSH) of peripheral monocytes (Mo) correlates positively with T cell infiltration within tumor islets and overall survival in patients with colorectal carcinoma. IcGSH redox status was determined in CD14(+) Mo prior to surgery by staining with monochlorobimane. The tumor-infiltrating T cells (TIL) were quantified as CD45RO(+) T cells in resected tumors using paraffin sections. A positive association was found between the GSH index and TIL in tumor islets (P < 0.001). The 50% cut-off value for the GSH index, that is the determinant between TIL presence or absence in tumor islets, was calculated to be almost 0.7 through logistic regression analysis. Mo with a GSH index of > or =0.7 were termed reductive (R)-Mo, and those with <0.7 were designated as oxidative (O)-Mo. Cox's proportional hazards regression analysis of patients with R-Mo or O-Mo prior to surgery, and the presence or absence of TIL, was found to correlate significantly with the overall survival rate of stage II and III patients. Kaplan-Meier analysis also showed a significant correlation. These results indicate that the Mo icGSH index is a useful biomarker parameter for better understanding the host/tumor relationship prior to surgery, thereby enabling the development of an individual patient-oriented therapeutic strategy.
仅使用外周血标本即可预测局部肿瘤生长部位的抗肿瘤免疫反应，这将有助于确定实体瘤患者的治疗选择。在这里，我们显示外周血单核细胞 (Mo) 中的谷胱甘肽细胞内含量 (icGSH) 与结直肠癌患者肿瘤胰岛内的 T 细胞浸润和总生存率呈正相关。在手术前，通过用单氯代丁烷染色来确定 CD14(+) Mo 中的 icGSH 氧化还原状态。使用石蜡切片在切除的肿瘤中定量肿瘤浸润的 T 细胞 (TIL) 作为 CD45RO(+) T 细胞。发现 GSH 指数与肿瘤胰岛中的 TIL 之间存在正相关 (P < 0.001)。通过逻辑回归分析计算出 GSH 指数的 50% 截止值，即肿瘤胰岛中 TIL 存在或不存在的决定因素，约为 0.7。GSH 指数> =0.7 的 Mo 被称为还原性 (R)-Mo，而 <0.7 的 Mo 被指定为氧化性 (O)-Mo。对术前具有 R-Mo 或 O-Mo 的患者以及 TIL 的存在与否进行 Cox 比例风险回归分析，发现与 II 期和 III 期患者的总生存率显著相关。Kaplan-Meier 分析也显示出显著相关性。这些结果表明，Mo icGSH 指数是一种有用的生物标志物参数，可在手术前更好地了解宿主/肿瘤关系，从而能够制定针对个体患者的治疗策略。
