The basic research on HIF-1-targeted cancer therapy

在这项研究中，我们研究了肿瘤组织中的缺氧可能与荷瘤宿主的免疫抑制有关的可能性。基于低氧诱导因子-1（HIF-1）调节与肿瘤进展相关的许多基因的表达的数据，我们假设在肿瘤组织中抑制HIF-1将增强抗肿瘤免疫应答。将HIF-1抑制剂施用到荷瘤小鼠的已建立的肿瘤中，然后检查在小鼠中引发的抗肿瘤免疫应答。结果，HIF-1抑制减弱了肿瘤组织中TGF-β的水平。在肿瘤引流淋巴结和脾脏中，调节细胞的数量减少。脾脏中抗原特异性效应细胞增多

In this study, we examined the possibility that hypoxia in tumor tissues might be implicated in the immunosuppression in tumor-bearing host. Based on the data that hypoxia-inducible factor-1 (HIF-1) regulates expressions of many genes associated with tumor progression, we hypothesized that inhibition of HIF-1 in tumor tissues would augment anti-tumor immune responses. Tumor-bearing mice were administered HIF-1 inhibitor into the established tumor, and then, anti-tumor immune responses elicited in the mice were examined. As results, HIF-1 inhibition attenuated the level of TGF-beta in tumor tissues. In tumor-draining lymph nodes and spleen, the numbers of regulatory cells were decreased. In spleen, antigen-specific effector cells were increased