肝细胞癌缺氧微环境中低氧诱导因子-1α促进癌细胞免疫逃逸及治疗耐受的发生机制

Mechanism for hypoxia inducible factor-1αto promote immune escape and therapeutic tolerance in hepatocellular carcinoma under hypoxic microenvironment

肝脏是机体最大的免疫器官,免疫耐受及逃避机制对肝细胞癌(hepatocellular carcinoma, HCC)的进展发挥着重要作用. HCC有着复杂的肿瘤微环境(tumormicroenvironment, TME), 研究TME中引起HCC细胞逃避机体免疫监视、产生治疗抗性的机制对HCC的临床治疗是很有必要的. 低氧诱导因子-1α (hypoxiainducible factor-1α, HIF-1α)是一种转录因子, 包含受缺氧调控的α亚基, 在缺氧环境中, 肿瘤细胞高表达HIF-1α, 参与肿瘤细胞增殖和转移、微血管生成、免疫逃逸以及治疗耐受等过程, 最终促进肿瘤的发生和发展. 在本文中, 我们将阐述缺氧TME中, HCC细胞激活HIF-1α的表达以促进癌细胞低氧适应, 调控免疫逃逸和治疗耐受的机制.

The liver is the largest immune organ in the body,and immunologic tolerance and escape mechanisms play an important role in hepatocellular carcinoma(HCC)development.HCC has a complex tumor microenvironment(TME),and it is necessary to study the mechanism that causes HCC cells to escape the body immune surveillance and produce therapeutic resistance in HCC clinical treatment.Hypoxia inducible factor-1α(HIF-1α)is a transcription factor that containsαsubunits regulated by hypoxia.Tumor cells highly express HIF-1αin a hypoxic environment,which participates in the processes of tumor cell proliferation and metastasis,microvascular production,immune escape,and therapeutic tolerance,ultimately promoting tumorigenesis and development.In this paper,we will elaborate on the mechanisms by which HCC cells activate HIF-1αexpression to promote hypoxic adaptation in cancer cells and regulate immune escape and treatment tolerance in hypoxic TME.