Shi Di, Jiang Peng
School of Life Sciences, Tsinghua University, Beijing, China.
Tsinghua-Peking Center for Life Sciences, Beijing, China.
Front Cell Dev Biol. 2021 Oct 18;9:762651. doi: 10.3389/fcell.2021.762651. eCollection 2021.
As a key transcription factor, the evolutionarily conserved tumor suppressor p53 (encoded by 53) plays a central role in response to various cellular stresses. A variety of biological processes are regulated by p53 such as cell cycle arrest, apoptosis, senescence and metabolism. Besides these well-known roles of p53, accumulating evidence show that p53 also regulates innate immune and adaptive immune responses. p53 influences the innate immune system by secreted factors that modulate macrophage function to suppress tumourigenesis. Dysfunction of p53 in cancer affects the activity and recruitment of T and myeloid cells, resulting in immune evasion. p53 can also activate key regulators in immune signaling pathways which support or impede tumor development. Hence, it seems that the tumor suppressor p53 exerts its tumor suppressive effect to a considerable extent by modulating the immune response. In this review, we concisely discuss the emerging connections between p53 and immune responses, and their impact on tumor progression. Understanding the role of p53 in regulation of immunity will help to developing more effective anti-tumor immunotherapies for patients with mutation or depletion.
作为一种关键的转录因子，进化上保守的肿瘤抑制因子p53（由TP53基因编码）在应对各种细胞应激时发挥着核心作用。p53调控多种生物学过程，如细胞周期阻滞、凋亡、衰老和代谢。除了这些p53的众所周知的作用外，越来越多的证据表明p53还调控先天性免疫和适应性免疫反应。p53通过分泌调节巨噬细胞功能以抑制肿瘤发生的因子来影响先天性免疫系统。癌症中p53功能失调会影响T细胞和髓样细胞的活性及募集，导致免疫逃逸。p53还可激活免疫信号通路中的关键调节因子，这些因子支持或阻碍肿瘤发展。因此，肿瘤抑制因子p53似乎在很大程度上通过调节免疫反应发挥其肿瘤抑制作用。在本综述中，我们简要讨论p53与免疫反应之间新出现的联系及其对肿瘤进展的影响。了解p53在免疫调节中的作用将有助于为有突变或缺失的患者开发更有效的抗肿瘤免疫疗法。
