J Clin Invest. 2024 Jun 17;134(12):e178540. doi: 10.1172/JCI178540.
Although cancer has long been considered a genetic disease, increasing evidence shows that epigenetic aberrations play a crucial role in affecting tumor biology and therapeutic response. The dysregulated epigenome in cancer cells reprograms the immune landscape within the tumor microenvironment, thereby hindering antitumor immunity, promoting tumor progression, and inducing immunotherapy resistance. Targeting epigenetically mediated tumor-immune crosstalk is an emerging strategy to inhibit tumor progression and circumvent the limitations of current immunotherapies, including immune checkpoint inhibitors. In this Review, we discuss the mechanisms by which epigenetic aberrations regulate tumor-immune interactions and how epigenetically targeted therapies inhibit tumor progression and synergize with immunotherapy.
虽然癌症长期以来一直被认为是一种遗传疾病,但越来越多的证据表明,表观遗传异常在影响肿瘤生物学和治疗反应方面起着至关重要的作用。癌细胞中失调的表观基因组重新编程了肿瘤微环境中的免疫景观,从而阻碍了抗肿瘤免疫、促进肿瘤进展并诱导免疫治疗耐药性。靶向表观遗传介导的肿瘤-免疫相互作用是一种抑制肿瘤进展和规避当前免疫疗法(包括免疫检查点抑制剂)局限性的新兴策略。在这篇综述中,我们讨论了表观遗传异常调节肿瘤-免疫相互作用的机制,以及表观遗传靶向治疗如何抑制肿瘤进展并与免疫治疗协同作用。