Sharp Stephen P, Avram Dorina, Stain Steven C, Lee Edward C
Department of Surgery, Albany Medical College, Albany, New York.
Department of Medicine, University of Florida, Gainesville, Florida.
J Surg Res. 2017 Feb;208:180-186. doi: 10.1016/j.jss.2016.09.038. Epub 2016 Sep 28.
Little is known about how the immunologic microenvironment changes during tumor progression and metastatic spread. Recently, murine models have shown the T-helper 17 (Th17) pathway to play an important role in promoting colorectal cancer (CRC). The purpose of this study was to compare cytokine profiles in the tumor microenvironment of CRC between local disease (stages I/II) and advanced disease (stages III/IV), and to determine whether these changes were manifest in the systemic circulation of patients with advanced disease.
Serum and tissue cytokine profiles were assayed among patients with documented adenocarcinoma before surgical resection at a single institution from September 2014 to February 2015. Using the Bio-Plex Pro Human Th17 Cytokine Assay Kit (Bio-Rad Laboratories), the concentrations of multiple cytokines were determined. Multiple logistic regression analyses were used to evaluate the association between TNM staging and cytokine levels.
A total of 33 patients with documented adenocarcinoma were included. None of the patients received neoadjuvant chemotherapy. American Joint Commission on Cancer TNM classification was used. Advanced disease was associated with elevated tumor levels of tumor necrosis factor-alpha, interleukin (IL)-4, IL-10, IL-17A, and IL-17F, and only stage IV showed elevated systemic levels of Th17-associated cytokines IL-17F, IL-23, and IL-25.
The Th17 pathway likely has important mechanistic implications in human CRC. Metastatic disease was associated with elevated Th17-associated cytokines both in colonic tissue and systemically. These changes in systemic expression of Th17-associated cytokines could establish novel pathways for CRC and warrant further investigation.
关于肿瘤进展和转移扩散过程中免疫微环境如何变化，人们了解甚少。最近，小鼠模型显示辅助性T细胞17（Th17）途径在促进结直肠癌（CRC）中起重要作用。本研究的目的是比较局部疾病（I/II期）和晚期疾病（III/IV期）的结直肠癌肿瘤微环境中的细胞因子谱，并确定这些变化是否在晚期疾病患者的全身循环中表现出来。
2014年9月至2015年2月在单一机构对手术切除前确诊为腺癌的患者进行血清和组织细胞因子谱分析。使用Bio-Plex Pro人Th17细胞因子检测试剂盒（伯乐生命医学产品公司）测定多种细胞因子的浓度。采用多因素逻辑回归分析评估TNM分期与细胞因子水平之间的关联。
共纳入33例确诊为腺癌的患者。所有患者均未接受新辅助化疗。采用美国癌症联合委员会TNM分类法。晚期疾病与肿瘤坏死因子-α、白细胞介素（IL）-4、IL-10、IL-17A和IL-17F的肿瘤水平升高有关，只有IV期显示Th17相关细胞因子IL-17F、IL-23和IL-25的全身水平升高。
Th17途径可能在人类结直肠癌中具有重要的机制意义。转移性疾病与结肠组织和全身Th17相关细胞因子升高有关。Th17相关细胞因子全身表达的这些变化可能为结直肠癌建立新的途径，值得进一步研究。
