SHS in Katowice, Department of Propaedeutics Surgery, Chair of General, Colorectal and Polytrauma Surgery, Medical University of Silesia in Katowice, Żeromskiego 7, 41-902, Bytom, Poland.
SHS in Katowice, Chair of General, Colorectal and Polytrauma Surgery, Medical University of Silesia in Katowice, Plac Medyków 1, 41-200, Sosnowiec, Poland.
Arch Immunol Ther Exp (Warsz). 2017 Oct;65(5):445-454. doi: 10.1007/s00005-017-0463-9. Epub 2017 Mar 25.
The aim of the study is the assessment of the intensity of the infiltration of tumor-associated macrophages (TAMs) CD68/iNOS and Tregs CD8/FoxP3 in colorectal cancer (CRC) patients as prognostic factors with respect to disease-free survival (DFS) and overall survival (OS). In this retrospective study, tissue samples were obtained from 89 patients undergoing resection for CRC (stage IIA, pT3N0M0 and stages IIIB and IIIC, pT3N1-2M0). Recurrence was observed in 45 patients at the time of the follow-up (10 local recurrences, 35 distant metastases). In patients with recurrence the following were present: a tendency to an older average age at the time of diagnosis (p = 0.07), higher nodal involvement (p = 0.002) and more advanced clinical disease (p = 0.01). The analysis of the clinical data and immunohistochemical studies were performed with the methodology of identification of TAM and Treg subsets in histological sections, with the aim to use it in routine clinical management. Both DSF and OS were the clinical parameters assessed in the study. The presence of intense infiltration of TAMs in the tumor stroma was related to shorter DFS (p = 0.005) and OS (p = 0.006). The opposite tendency was observed in the tumor front (p = 0.061). The relative risks of recurrence and cancer-related death were more than twice higher in the group of patients with intense infiltration of TAMs in the tumor stroma (RR 2.05, 95% CI 1.33-3.14; p = 0.001 and RR 2.08, 95% CI 1.28-3.39; p = 0.003, respectively). Intense infiltration of Tregs in the tumor stroma was related to shorter DFS and OS (p < 0.0001). The relative risks of recurrence and death in a group of patients with intense infiltration of Tregs in the tumor stroma were more than 12 times higher than in patients with less intense infiltration (RR 12.3, 95% CI 5.44-27.9; p < 0.0001 and RR 12.5, 95% CI 4.9-32.4; p < 0.0001, respectively). Infiltration of TAMs CD68/iNOS and Tregs CD8/FoxP3 in the tumor stroma are negative prognostic factors with a positive correlation between them. Tregs may constitute an independent prognostic factor in patients with CRC.
本研究的目的是评估肿瘤相关巨噬细胞（TAMs）CD68/iNOS 和调节性 T 细胞（Tregs）CD8/FoxP3 在结直肠癌（CRC）患者中的浸润强度作为无病生存（DFS）和总生存（OS）的预后因素。在这项回顾性研究中，从 89 名接受 CRC 切除术的患者中获得组织样本（IIA 期，pT3N0M0 和 IIIB 期和 IIIC 期，pT3N1-2M0）。在随访时观察到 45 例患者复发（10 例局部复发，35 例远处转移）。在复发患者中存在以下情况：诊断时平均年龄偏大的趋势（p=0.07）、淋巴结受累程度更高（p=0.002）和临床疾病更晚期（p=0.01）。使用组织学切片中 TAM 和 Treg 亚群的鉴定方法进行临床数据和免疫组织化学研究，目的是在常规临床管理中使用该方法。DFS 和 OS 是本研究中评估的临床参数。肿瘤基质中 TAMs 的浸润强度与较短的 DFS（p=0.005）和 OS（p=0.006）相关。在肿瘤前缘观察到相反的趋势（p=0.061）。在肿瘤基质中 TAMs 浸润强度较高的患者中，复发和癌症相关死亡的相对风险高两倍以上（RR 2.05，95%CI 1.33-3.14；p=0.001 和 RR 2.08，95%CI 1.28-3.39；p=0.003）。肿瘤基质中 Tregs 的浸润强度与较短的 DFS 和 OS 相关（p<0.0001）。肿瘤基质中 Tregs 浸润强度较高的患者中，复发和死亡的相对风险比浸润强度较低的患者高 12 倍以上（RR 12.3，95%CI 5.44-27.9；p<0.0001 和 RR 12.5，95%CI 4.9-32.4；p<0.0001）。肿瘤基质中 TAMs CD68/iNOS 和 Tregs CD8/FoxP3 的浸润是负预后因素，它们之间呈正相关。Tregs 可能是 CRC 患者的独立预后因素。
