Zou Q, Hu B, Yu H C, Ren D L
Department of Colorectal and Anal Surgery, The Sixth Affiliated Hospital, Sun Yet-sen University, Guangzhou 510655, China Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China.
Department of Colorectal and Anal Surgery, The Sixth Affiliated Hospital, Sun Yet-sen University, Guangzhou 510655, China.
Zhonghua Wei Chang Wai Ke Za Zhi. 2021 Dec 25;24(12):1086-1092. doi: 10.3760/cma.j.cn441530-20210402-00144.
As cytotoxic T cells, CD8+ T lymphocytes can kill tumor cells by releasing perforin and other effector molecules, but the correlation between their infiltration level and the prognosis of colorectal cancer varies in previous studies. This study aims to explore the distribution of CD8+T cells in tumor center and invasive margin of colorectal cancer, and to analyze their correlation with the prognosis of patients. A retrospective cohort study was used to analyze the clinicopathological features of 221 patients with colorectal cancer from the colorectal cancer pathological database of the Sixth Affiliated Hospital of Sun Yat-sen University between 2009 and 2012. Case inclusion criteria: (1) colorectal cancers confirmed by postoperative pathology; (2) patients with follow-up data. Exclusion criteria: (1) multiple primary cancers; (2) inflammatory bowel disease, Lynch syndrome or familial adenomatous polyposis; (3) no available paraffin slides; (4) patients receiving preoperative radiotherapy or chemotherapy. A total of 221 patients met the criteria. Immunohistochemical staining was used to count the CD8+ T cells in tumor center and invasive margin in the paraffin slides. Meanwhile the relative expression of CD8B gene in 22 fresh freeze samples of colorectal cancer was detected. Then the correlation of the expression with CD8+T cell density was examined. The patients were divided into high and low infiltration groups according to the level of CD8+T cells. Log-rank test was applied to compare the overall survival of the two groups of patients, and Cox regression analysis was used to adjust the prognostic significance of CD8+T cell infiltration. There were 118 males and 103 females. In 221 slides, CD8+T cells infiltrating in invasive margin were more than those in tumor center [median (range): 37(0-141) / field vs. 14(0-106) / field, =-11.985, <0.001], and the number of CD8+T cell in the tumor center was positively correlated with those in invasive margin (=0.610, <0.001). The number of CD8+ T cell in tumor center was positively correlated with the relative expression of CD8B gene (=0.524, =0.012). Survival analysis showed that the overall survival of the high infiltration group was better than that of the low infiltration group both in tumor center and invasive margin (median survival: 84.1 months vs. 73.5 months, <0.001; 84.2 months vs. 75.9 months, =0.002). Cox regression analysis revealed that high CD8+T cell infiltration in tumor center was an independent protective factor of overall survival (HR=0.369, 95% CI: 0.168-0.812, =0.013). The infiltration level of CD8+T cells in tumor center is lower than that in invasive margin, and they are positively correlated. The level of CD8+ T cell infiltration in tumor center is related to overall survival and can be used as a potential pronostic marker.
作为细胞毒性T细胞,CD8 + T淋巴细胞可通过释放穿孔素和其他效应分子来杀伤肿瘤细胞,但在以往研究中,其浸润水平与结直肠癌预后的相关性存在差异。本研究旨在探讨CD8 + T细胞在结直肠癌肿瘤中心和浸润边缘的分布情况,并分析其与患者预后的相关性。采用回顾性队列研究,分析2009年至2012年中山大学附属第六医院结直肠癌病理数据库中221例结直肠癌患者的临床病理特征。病例纳入标准:(1)术后病理确诊为结直肠癌;(2)有随访数据的患者。排除标准:(1)多原发性癌;(2)炎症性肠病、林奇综合征或家族性腺瘤性息肉病;(3)无可用石蜡切片;(4)接受术前放疗或化疗的患者。共有221例患者符合标准。采用免疫组织化学染色法对石蜡切片中肿瘤中心和浸润边缘的CD8 + T细胞进行计数。同时检测22例新鲜冷冻的结直肠癌样本中CD8B基因的相对表达。然后检测该表达与CD8 + T细胞密度的相关性。根据CD8 + T细胞水平将患者分为高浸润组和低浸润组。采用对数秩检验比较两组患者的总生存期,并采用Cox回归分析调整CD8 + T细胞浸润的预后意义。男性118例,女性103例。在221张切片中,浸润边缘的CD8 + T细胞多于肿瘤中心[中位数(范围):37(0 - 141)/视野 vs. 14(0 - 106)/视野,=-11.985,<0.001],肿瘤中心的CD8 + T细胞数量与浸润边缘的呈正相关(=0.610,<0.001)。肿瘤中心CD8 + T细胞数量与CD8B基因的相对表达呈正相关(=0.524,=0.012)。生存分析显示,高浸润组在肿瘤中心和浸润边缘的总生存期均优于低浸润组(中位生存期:84.1个月 vs. 73.5个月,<0.001;84.2个月 vs. 75.9个月,=0.002)。Cox回归分析显示,肿瘤中心高CD8 + T细胞浸润是总生存期的独立保护因素(HR = 0.369,95%CI:0.168 - 0.812,=0.013)。肿瘤中心CD8 + T细胞的浸润水平低于浸润边缘,且二者呈正相关。肿瘤中心CD8 + T细胞浸润水平与总生存期相关,可作为潜在的预后标志物。