Mûzes Györgyi, Sipos Ferenc
II. Sz. Belgyógyászati Klinika, Semmelweis Egyetem, Budapest, Hungary.
Magy Onkol. 2016 Mar 2;60(1):55-63. Epub 2016 Jan 4.
According to recent data, the involvement of autophagy in tumor development is unquestionable. Nevertheless, cell-derived pathogen/danger-associated molecular pattern (PAMP/DAMP)-sensing Toll-like receptors (TLRs) are also able to contribute to tumorigenesis and immune escape of malignantly transformed cells. Besides immunocompetent cells, several types of tumors also exhibit TLRs. TLR- and autophagy-related signaling pathways, on the other hand, may evolve anti-tumor effects in a context dependent cell- and microenvironment-specific mode. Nowadays, the autophagy machinery has been considered as a crucial homeostatic process of eukaryotic cells, and as essential constituent of the immune system influencing antimicrobial and inflammation-related immune responses. Accumulating evidence indicates that TLRs and autophagy are interdependent in response to PAMPs and DAMPs, in addition there is a bi-directional controling cross-modulation between them. Regarding personalized medicine, theoretically, it is reasonable that manipulation of the TLR-autophagy regulatory loop might be adaptable for anti-cancer therapy.
根据最近的数据,自噬参与肿瘤发展是毋庸置疑的。然而,细胞源性病原体/危险相关分子模式(PAMP/DAMP)传感的Toll样受体(TLR)也能够促进恶性转化细胞的肿瘤发生和免疫逃逸。除了免疫活性细胞外,几种类型的肿瘤也表达TLR。另一方面,TLR和自噬相关信号通路可能以依赖于细胞和微环境的特定模式发挥抗肿瘤作用。如今,自噬机制已被认为是真核细胞的关键稳态过程,也是影响抗菌和炎症相关免疫反应的免疫系统的重要组成部分。越来越多的证据表明,TLR和自噬在对PAMP和DAMP的反应中相互依赖,此外它们之间存在双向的调控交叉调节。关于个性化医疗理论上,操纵TLR-自噬调节环可能适用于抗癌治疗是合理的。