Sonnessa Margherita, Cioffi Antonella, Brunetti Oronzo, Silvestris Nicola, Zito Francesco A, Saponaro Concetta, Mangia Anita
Functional Biomorphology Laboratory, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy.
Medical Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy.
Front Oncol. 2020 Sep 4;10:1587. doi: 10.3389/fonc.2020.01587. eCollection 2020.
The tumor microenvironment (TME) is crucial in cancer onset, progression and response to treatment. It is characterized by an intricate interaction of immune cells and cytokines involved in tumor development. Among these, inflammasomes are oligomeric molecular platforms and play a key role in inflammatory response and immunity. Inflammasome activation is initiated upon triggering of pattern recognition receptors (Toll-like receptors, NOD-like receptors, and Absent in melanoma like receptors), on the surface of immune cells with the recruitment of caspase-1 by an adaptor apoptosis-associated speck-like protein. This structure leads to the activation of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 and participates in different biological processes exerting its effects. To date, the Nod-Like Receptor Protein 3 (NLRP3) inflammasome has been well studied and its involvement has been established in different cancer diseases. In this review, we discuss the structure, biology and mechanisms of inflammasomes with a special focus on the specific role of NLRP3 in breast cancer (BC) and in the sub-group of triple negative BC. The NLRP3 inflammasome and its down-stream pathways could be considered novel potential tumor biomarkers and could open new frontiers in BC treatment.
肿瘤微环境（TME）在癌症的发生、发展及对治疗的反应中起着至关重要的作用。其特征在于参与肿瘤发展的免疫细胞和细胞因子之间存在复杂的相互作用。其中，炎性小体是寡聚分子平台，在炎症反应和免疫中发挥关键作用。炎性小体的激活是在免疫细胞表面的模式识别受体（Toll样受体、NOD样受体和黑色素瘤缺失样受体）被触发后启动的，衔接蛋白凋亡相关斑点样蛋白会募集半胱天冬酶-1。这种结构导致促炎细胞因子白细胞介素（IL）-1β和IL-18的激活，并参与发挥其作用的不同生物学过程。迄今为止，Nod样受体蛋白3（NLRP3）炎性小体已得到充分研究，并且其在不同癌症疾病中的作用也已明确。在本综述中，我们讨论炎性小体的结构、生物学特性和机制，特别关注NLRP3在乳腺癌（BC）和三阴性BC亚组中的具体作用。NLRP3炎性小体及其下游途径可被视为新型潜在肿瘤生物标志物，并可能为BC治疗开辟新的前沿领域。
