Laboratory of Molecular Genetics, Chromosome Stability Section, National Institute of Environmental Health Sciences, National Institutes of Health, North Carolina 27709, USA.
Curr Opin Oncol. 2013 Jan;25(1):85-92. doi: 10.1097/CCO.0b013e32835b6386.
The p53 tumor suppressor is a master regulator of antitumor defenses through its control of growth arrest, senescence and apoptosis. In recent years, p53 regulation was found to extend to a variety of biological processes including autophagy, fertility, metabolism and immune responses. Here, we focus on the role of p53 in the immune system. We explore the relationship between p53 and the innate immune response with particular emphasis on the Toll-like receptor (TLR) pathway and implications for cancer therapy.
Numerous studies have shown that the immune system, especially innate immunity, has a critical role in tumor development. It appears that p53 can influence innate immune responses as part of its tumor suppressor activities and recent work suggests that the complete set of innate immune TLR genes are responsive to chromosomal stress and the transcriptional network regulated by p53. Activation of p53 by common antitumor agents results in p53 dependent regulation of expression of most TLR genes in human primary and cancer cell lines, resulting in modulation of TLR downstream responses to cognate ligands. In addition several tumor-associated p53 mutants can also affect TLR gene expression. These observations together with the discovery of other immune-related p53 target genes provide new insights into the relationship between p53 and immunity and suggest approaches that might be useful in cancer therapies.
The tumor suppressor p53 can modulate innate immune gene responses in response to factors that can activate p53. This is expected to provide new opportunities in cancer diagnosis and in chemotherapeutic strategies that employ specific TLR agonists or antagonists that target the TLR pathway.
综述目的：p53 肿瘤抑制因子通过控制细胞生长停滞、衰老和凋亡，成为抗肿瘤防御的主要调控因子。近年来，发现 p53 的调控作用延伸到多种生物学过程，包括自噬、生育、代谢和免疫反应。在这里，我们重点关注 p53 在免疫系统中的作用。我们探讨了 p53 与先天免疫反应的关系，特别强调了 Toll 样受体 (TLR) 途径及其对癌症治疗的影响。
最新发现：大量研究表明，免疫系统，特别是先天免疫系统，在肿瘤发生发展中起着关键作用。似乎 p53 可以通过其作为肿瘤抑制因子的活动来影响先天免疫反应，最近的工作表明，完整的先天免疫 TLR 基因对染色体应激和由 p53 调节的转录网络有反应。常见抗肿瘤药物激活 p53 会导致人类原代细胞和癌细胞系中大多数 TLR 基因的 p53 依赖性表达调节，从而调节对同源配体的 TLR 下游反应。此外，几种肿瘤相关的 p53 突变体也可以影响 TLR 基因的表达。这些观察结果以及对其他免疫相关 p53 靶基因的发现，为 p53 与免疫之间的关系提供了新的见解，并为癌症诊断和采用特定 TLR 激动剂或拮抗剂靶向 TLR 途径的化疗策略提供了新的机会。
总结：肿瘤抑制因子 p53 可以在激活 p53 的因素作用下调节先天免疫基因反应。这有望为癌症诊断和采用特定 TLR 激动剂或拮抗剂靶向 TLR 途径的化疗策略提供新的机会。
