Mikulandra Martina, Pavelic Jasminka, Glavan Tanja Matijevic
Department of Radiotherapy and Medical Oncology, University Hospital Centre Sisters of Mercy, Zagreb. Croatia.
Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb. Croatia.
Curr Med Chem. 2017;24(19):2011-2032. doi: 10.2174/0929867324666170320114359.
The immune system's first line of defense is innate immunity, largely based on a large family of pattern recognition receptors (PRRs) that recognize evolutionary conserved molecular motifs on pathogens called pathogen-associated molecular patterns (PAMPs). The most extensively studied family of PRRs is Toll-like receptors (TLRs), which can trigger various cellular pathways after ligand stimulation. Their role in cancer is still unresolved as there are many different studies showing contradictory results. TLRs have been associated with both tumor progression and immunosuppression as well as with apoptosis and immune system activation. With their ability to induce apoptotic response and activation of innate and adaptive immunity, TLRs are an interesting pharmacological target for the development of anticancer therapy. There are numerous studies including the clinical trials reviewed in this paper, indicating that TLR agonists, especially combined with other more conventional therapies such as chemotherapy and radiotherapy, are promising adjuvants or components of newly developed treatment regimens. Still, the increasing number of studies indicating protumorigenic consequences of TLR activation in various cancer types and recent reports of the existence of endogenous TLR ligands, forewarn that more studies on this topic are required before their inclusion into regular clinical practice.
免疫系统的第一道防线是固有免疫，主要基于一大类模式识别受体（PRR），这些受体识别病原体上进化保守的分子基序，即病原体相关分子模式（PAMP）。研究最为广泛的PRR家族是Toll样受体（TLR），其在配体刺激后可触发各种细胞途径。它们在癌症中的作用仍未明确，因为许多不同的研究显示出相互矛盾的结果。TLR与肿瘤进展、免疫抑制以及细胞凋亡和免疫系统激活均有关联。由于TLR能够诱导凋亡反应并激活固有免疫和适应性免疫，因此是开发抗癌疗法的一个有吸引力的药理学靶点。包括本文所综述的临床试验在内，有大量研究表明，TLR激动剂，尤其是与化疗和放疗等其他更传统疗法联合使用时，是很有前景的辅助剂或新开发治疗方案的组成部分。尽管如此，越来越多的研究表明TLR激活在各种癌症类型中会产生促肿瘤后果，而且最近有报道称存在内源性TLR配体，这警示在将其纳入常规临床实践之前，还需要对该主题进行更多研究。
