不同肿瘤相关成纤维细胞亚群的临床意义及与免疫治疗耐药关系的研究  

Clinical significance of cancer fibroblast associated subpopulations and their relationship with immune therapy resistance effects

作　　者：刘磊 刘金涛[1] 孔锦[2] Liu Lei;Liu Jintao;Kong Jin(Department of Internal Medicine NO.3,Tumor Hospital of Jinjing,Jining 272000,China;Internal Medicine,Medical Oncology,the Affiliated Hospital of Jining Medical College,Jining 272000,China)

机构地区：[1]济宁肿瘤医院内三科,山东济宁272000 [2]济宁医学院附属医院肿瘤内科,山东济宁272000

出　　处：《国际免疫学杂志》2023年第6期642-646,共5页International Journal of Immunology

摘　　要：目的分析不同的肿瘤相关成纤维细胞亚群的临床意义和免疫治疗有关耐药效应。方法在TCGA数据库内提取98例恶性肿瘤患者信息,采用单样本基因功能富集分析(single sample gene set enrichment analysis,ssGSEA)肿瘤患者成纤维细胞有关亚群相对浸润丰度情况,Log-Rank检验分析成纤维细胞亚群和免疫标志物间的关系。结果不同肿瘤患者各成纤维细胞分布存在较高的异质性,多数患者成纤维细胞的整体丰度处在较高水平,少数患者处在较低水平。与男性患者比较,第5及第6亚群更多富集于女性患者(P值分别为0.005,0.003);随吸烟时间延长,肿瘤患者中第6亚群占比不断降低,且第6亚群浸润丰度于早期肿瘤中水平更高;第1和第2亚群多富集于未转移患者(P值分别为0.029,0.021)。不同的成纤维细胞有关亚群对患者预后的影响存在差异,其中第6亚群为患者预后的保护因子(P=0.014),可能对肿瘤有关干性微环境生成和维持起到抑制作用;另5个亚群可能介导免疫治疗耐药和肿瘤干性微环境的维持。结论不同的成纤维细胞有关亚群有着不同生物学特征,临床上通过调节各亚群在肿瘤患者中的比例,可能改善肿瘤患者预后,降低免疫治疗耐药的发生。Objective To analyze the clinical significance of cancer associated fibroblast related subpopulations and the drug resistance effects related to immunotherapy.Methods The information of 98 patients with malignant tumor was extracted from the TCGA database,and the relative infiltration abundance of the relevant subsets of fibroblasts of tumor patients was analyzed by single sample gene set enrichment analysis(ssGSEA).The relationship between fibroblast subsets and immune markers was analyzed by Log-Rank assay.Results There was high heterogeneity in the distribution of fibroblasts in patients with different tumors,and the overall abundance of fibroblasts in most patients was at a high level,while a few patients were at a low level.Compared with male patients,the 5th and 6th subgroups were more enriched in female patients(P values were 0.005 and 0.003,respectively).With the extension of smoking time,the proportion of subgroup 6 in tumor patients decreased continuously,and the infiltration abundance of subgroup 6 was higher in early tumors.Subgroups 1 and 2 were mostly enriched in patients without metastasis(P values were 0.029 and 0.021,respectively).Different fibroblast related subgroups have different effects on the prognosis of patients,and the sixth subgroup is a prognostic protective factor(P=0.014),which may inhibit the formation and maintenance of tumor-related dry microenvironment.Another five subgroups may mediate immunotherapy resistance and maintenance of tumor dry microenvironment.Conclusion Different subpopulations of fibroblasts have different biological characteristics.Accurately adjusting the proportion of each subpopulation in tumor patients in clinical practice may improve the prognosis of tumor patients and reduce immune therapy resistance.

关 键 词：成纤维细胞有关亚群 免疫治疗 耐药 免疫学效应 恶性肿瘤 

分 类 号：R730.51[医药卫生—肿瘤]