髓系免疫细胞在肝细胞癌中标记基因的鉴定及免疫特征

Identification of Marker Genes and Immune Characterization of Myeloid-Derived Suppressor Cells in Hepatocellular Carcinoma

摘要: 目的：肝细胞癌(HCC)是全球第四大癌症相关死亡原因，且治疗选择有限。髓源免疫抑制细胞(MDSC)是在肿瘤微环境中(TME)中表现为免疫抑制活性的细胞群。在肝细胞癌中少有对MDSC特征标记的研究，同时缺少评价MDSC与免疫治疗关系的研究。方法：我们以肝细胞癌的单细胞数据为基础，鉴定了肝细胞癌的标记基因。进一步联合TCGA的数据开发了MDSC评分工具并探究与免疫治疗的关系。结果：我们鉴定了肝细胞癌中MDSC的11个特征基因，并基于此开发了一种ssGSEA工具评价MDSC的浸润。我们发现MDSC浸润影响患者预后并对免疫治疗具有抵抗作用。结论：肝细胞癌中MDSC的浸润对预后和免疫治疗具有不良影响。

Abstract: Objective: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide and has limited treatment options. Myeloid-derived immunosuppressive cells (MDSC) are a population of cells that exhibit immunosuppressive activity in the tumor microenvironment (TME). There are few studies of MDSC signature markers in hepatocellular carcinoma, as well as a lack of studies evaluating the relationship between MDSC and immunotherapy. Methods: We identified marker genes for MDSC based on single-cell data in hepatocellular carcinoma. We further developed an MDSC scoring tool using TCGA data and explored the relationship with immunotherapy. Results: We identified 11 genes that characterize MDSC in hepatocellular carcinoma and developed a ssGSEA tool based on them to evaluate MDSC infiltration. We found that MDSC infiltration affected patient prognosis and was resistant to immunotherapy. Conclusion: Infiltration of MDSC in hepatocellular carcinoma has an adverse effect on prognosis and immunotherapy.