结直肠癌的免疫微环境研究

Characterization of the Colorectal Cancer Tumor Immune Microenvironment

目的免疫微环境在多种肿瘤中进行了研究,但是针对结直肠癌免疫微环境的研究还是不多。方法 Gene Expression Omnibus (GEO)数据库中下载表达谱数据集分别是GSE42284(n=188)和GSE24551(n=160)以及The Cancer Genome Atlas (TCGA)数据库(n=437),基于ssGSEA解析出来29种免疫的细胞、免疫因子和免疫通络的丰度进行层次聚类。结果结直肠癌中的免疫微环境分为高中低免疫组,能够在独立数据集中验证。T cells CD8、T cells follicular helper、Macrophages M1和Dendritic cells resting等免疫细胞的丰度在高免疫组高于低免疫组。然而Macrophages M0、Macrophages M2、T cells CD4 memory resting等免疫细胞在高免疫组低于免疫组。产生IGA的肠道免疫网络,自然杀伤细胞介导的细胞毒性,toll样受体信号通路和造血细胞等通路在高免疫组的活性显著高于低免疫组,高免疫组与低免疫组比CD274和CTLA4的表达显著性的增加。结论结直肠免疫微环境有高中低免疫分组,且高免疫组患者处于免疫激活转态。因此,根据我们筛选出来的高免疫组患者,可尝试PD-L1免疫抑制剂治疗的探索研究。

Objective A huge impact on the immunotherapy is exerted by the immune environment of the principal tumor.That being said,the immune environment's clinical relevance in Colorectal cancer(CRC)is largely unknown.Methods The gene expression profiles of CRC two cohorts GEO(Gene Expression Omnibus,GSE42284)(n=188)and GSE24551(n=160),and TCGA(Cancer Genome Atlas,n=437)were utilized in the present study.Using three publicly available CRC expression datasets,29 immune signatures were expression profiled,and on this basis,The classification was conducted using the hierarchical clustering method.Results By identifying three CRC subtypes L,M,and H representing Immunity Low,Immunity Medium and Immunity High,respectively,we showed that this segregation gave enhanced prognosis,was reliable and was done by examining different datasets.Immune_H had a better prognostic outcome as well as a higher immune score.In CRC,potentially positive associations between immune and pathway activities were displayed.The enriching of Intestinal immune network for IGA production,Natural killer cell mediated cytotoxicity Toll like receptor signal pathway Hematopolietic cell lineage were high in Immunity High vs Immunity Low subtypes.T cells CD8,T cells follicular helper,Macrophages M1,Dendritic cells resting were higher in Immunity High than Immunity Low subtype.While,Macrophages M0,Macrophages M2,T cells CD4 memory resting were lower in Immunity High than Immunity Low subtype.The expression of CD274 and CTLA4 were higher in Immunity High vs Immunity Low subtypes.Conclusions CRC Treatment has potential clinical implications because of the immune expression based-identification of CRC subtypes.