Obesity is a well-established risk factor for colorectal cancer (CRC), but the association with the tumor microenvironment has been sparsely described. Herein, we examined the relationship between pre-diagnostic anthropometry and CRC risk according to tumor immune cell composition, with particular reference to potential sex differences. The density of different immune cell subsets was assessed by immunohistochemistry in tissue microarrays with tumors from 584 incident CRC cases in a prospective, population-based cohort (n = 28098). Multivariable Cox regression models, adjusted for age, smoking, alcohol intake, and educational level, were applied to calculate risk of immune marker-defined CRC in relation to quartiles of pre-diagnostic height, weight, body mass index (BMI), waist and hip circumferences, waist-hip ratio (WHR), and body fat percentage (BFP). Obesity was all over significantly associated with risk of CRC with low density of FoxP3+ T cells and low programmed cell-death protein 1 (PD-L1) expression on tumor cells, but with high density of CD8+ T cells and CD20+ B cells. In women, obesity was significantly associated with risk of PD-L1 high tumors (p= 0.009 for weight, p= 0.039 for BMI). Contrastingly, in men, obesity defined by all anthropometric factors was significantly associated with PD-L1 low tumors (p= 0.005 for weight, p = 0.002 for BMI, p<0.001 for waist, p= 0.011 for hip, p<0.001 for WHR, and p= 0.004 for BFP). In summary, obesity appears to influence the immune landscape of CRC, possibly in a sex-dependent manner. Thus, anthropometry and sex may be important factors to take into account when assessing the prognostic or predictive value of relevant complementary immune biomarkers.

译文

肥胖是结直肠癌 (CRC) 的公认危险因素,但与肿瘤微环境的关系很少被描述。在此,我们根据肿瘤免疫细胞组成,特别是潜在的性别差异,研究了诊断前人体测量学与CRC风险之间的关系。在前瞻性,基于人群的队列 (n = 28098) 中,通过组织微阵列中具有来自584例CRC病例的肿瘤的组织微阵列中评估了不同免疫细胞亚群的密度。根据年龄,吸烟,饮酒和受教育程度进行调整的多变量Cox回归模型用于计算免疫标记物定义的CRC的风险,该风险与诊断前身高,体重,体重指数 (BMI),腰围和臀围的四分位数有关。腰臀比 (WHR) 和体脂百分比 (BFP)。肥胖与CRC的风险显着相关,其中FoxP3 T细胞密度低,肿瘤细胞上程序性细胞死亡蛋白1 (PD-L1) 表达低,而CD8 T细胞和CD20 b细胞密度高。在女性中,肥胖与PD-L1高肿瘤的风险显着相关 (体重p = 0.009,BMI p = 0.039)。相反,在男性中,由所有人体测量因素定义的肥胖与PD-L1低肿瘤显着相关 (体重p = 0.005,BMI p = 0.002,腰围p<0.001,臀部p = 0.011,WHR p<0.001,BFP p = 0.004)。总之,肥胖似乎以性别依赖的方式影响CRC的免疫环境。因此,人体测量学和性别可能是评估相关补充免疫生物标志物的预后或预测价值时要考虑的重要因素。

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