Vascular Program, Institute for Cell Engineering; and Departments of Genetic Medicine, Pediatrics, Oncology, Radiation Oncology, Medicine, and Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Physiology (Bethesda). 2021 Mar 1;36(2):73-83. doi: 10.1152/physiol.00034.2020.
Activation of the innate and adaptive immune systems represents a promising strategy for defeating cancer. However, during tumor progression, cancer cells battle to shift the balance from immune activation to immunosuppression. Critical sites of this battle are regions of intratumoral hypoxia, and a major driving force for immunosuppression is the activity of hypoxia-inducible factors, which regulate the transcription of large batteries of genes in both cancer and stromal cells that block the infiltration and activity of cytotoxic T lymphocytes and natural killer cells, while stimulating the infiltration and activity of regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages. Targeting hypoxia-inducible factors or their target gene products may restore anticancer immunity and improve the response to immunotherapies.
先天免疫和适应性免疫系统的激活代表了战胜癌症的一种有前途的策略。然而，在肿瘤进展过程中，癌细胞会努力改变免疫激活和免疫抑制之间的平衡。这场战斗的关键部位是肿瘤内缺氧区域，而免疫抑制的一个主要驱动力是缺氧诱导因子的活性，它调节癌细胞和基质细胞中大量基因的转录，这些基因阻止细胞毒性 T 淋巴细胞和自然杀伤细胞的浸润和活性，同时刺激调节性 T 细胞、髓系来源的抑制细胞和肿瘤相关巨噬细胞的浸润和活性。靶向缺氧诱导因子或其靶基因产物可能恢复抗肿瘤免疫并改善免疫治疗的反应。
