Yoshida Naohiro, Kinugasa Tetsushi, Miyoshi Hiroaki, Sato Kensaku, Yuge Kotaro, Ohchi Takafumi, Fujino Shinya, Shiraiwa Sachiko, Katagiri Mitsuhiro, Akagi Yoshito, Ohshima Koichi
Department of Surgery, Kurume University School of Medicine, Kurume-shi, Fukuoka, Japan.
Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Ann Surg Oncol. 2016 Mar;23(3):919-27. doi: 10.1245/s10434-015-4923-3. Epub 2015 Nov 12.
Tumor-infiltrating lymphocytes (TILs), part of the host immune response, have been widely reported as influential factors in the tumor microenvironment for the clinical outcome of colorectal cancer (CRC). However, the network of helper T cells is very complex, and which T-cell subtypes affect the progression of CRC and postoperative prognosis remains unclear. This study investigated the expression of several subtypes of TILs including T helper type 1 (Th1), Th2, Th17, and regulatory T (Treg) cells to determine their correlation with clinicopathologic features and postoperative prognosis.
The study investigated the expression of TILs using immunohistochemistry of tissue microarray samples for 199 CRC patients. The number of each T-cell subtype infiltrating tumors was counted using ImageJ software. The relationship between TIL marker expression, clinicopathologic features, and prognosis was analyzed.
A high RORγT/CD3 ratio (Th17 ratio) was significantly correlated with lymph node metastasis (p = 0.002), and a high of Foxp3/CD3 ratio (Treg ratio) was correlated with tumor location in the colon (p = 0.04), as shown by the Chi square test. In multivariate analysis, a high RORγT/CD3 ratio was the only independent prognostic factor for overall survival (p = 0.04; hazard ratio [HR], 1.84; 95% confidence interval [CI] 1.02-3.45).
This study confirmed a high RORγT/CD3 ratio as a strong prognostic marker for postoperative survival. The immunohistochemistry results suggest that Th17 may affect lymph node metastasis in CRC. If new immunotherapies reducing Th17 expression are established, they may improve the efficiency of cancer treatment and prolong the survival of patients with CRC.
肿瘤浸润淋巴细胞（TILs）作为宿主免疫反应的一部分，已被广泛报道为影响结直肠癌（CRC）临床结局的肿瘤微环境中的重要因素。然而，辅助性T细胞网络非常复杂，哪种T细胞亚型影响CRC的进展及术后预后仍不清楚。本研究调查了包括1型辅助性T细胞（Th1）、Th2、Th17和调节性T（Treg）细胞在内的几种TILs亚型的表达，以确定它们与临床病理特征及术后预后的相关性。
本研究采用免疫组织化学方法检测了199例CRC患者组织芯片样本中TILs的表达。使用ImageJ软件对浸润肿瘤的每种T细胞亚型的数量进行计数。分析了TIL标志物表达、临床病理特征和预后之间的关系。
卡方检验显示，高RORγT/CD3比值（Th17比值）与淋巴结转移显著相关（p = 0.002），高Foxp3/CD3比值（Treg比值）与结肠肿瘤位置相关（p = 0.04）。多因素分析显示，高RORγT/CD3比值是总生存的唯一独立预后因素（p = 0.04；风险比[HR]，1.84；95%置信区间[CI] 1.02 - 3.45）。
本研究证实高RORγT/CD3比值是术后生存的强有力预后标志物。免疫组织化学结果表明，Th17可能影响CRC的淋巴结转移。如果建立新的降低Th17表达的免疫疗法，可能会提高癌症治疗效率并延长CRC患者的生存期。
