Burn Olivia K, Prasit Kef K, Hermans Ian F
Malaghan Institute of Medical Research, P.O. Box 7060, Wellington 6042, New Zealand.
Maurice Wilkins Centre, Private Bag 92019, Auckland 1042, New Zealand.
Cancers (Basel). 2020 Dec 18;12(12):3824. doi: 10.3390/cancers12123824.
Signalling through pattern recognition receptors (PRRs) leads to strong proinflammatory responses, enhancing the activity of antigen presenting cells and shaping adaptive immune responses against tumour associated antigens. Unfortunately, toxicities associated with systemic administration of these agonists have limited their clinical use to date. Direct injection of PRR agonists into the tumour can enhance immune responses by directly modulating the cells present in the tumour microenvironment. This can improve local antitumour activity, but importantly, also facilitates systemic responses that limit tumour growth at distant sites. As such, this form of therapy could be used clinically where metastatic tumour lesions are accessible, or as neoadjuvant therapy. In this review, we summarise current preclinical data on intratumoural administration of PRR agonists, including new strategies to optimise delivery and impact, and combination studies with current and promising new cancer therapies.
通过模式识别受体（PRR）发出的信号会引发强烈的促炎反应，增强抗原呈递细胞的活性，并塑造针对肿瘤相关抗原的适应性免疫反应。不幸的是，与全身给药这些激动剂相关的毒性限制了它们迄今为止的临床应用。将PRR激动剂直接注射到肿瘤中可以通过直接调节肿瘤微环境中存在的细胞来增强免疫反应。这可以提高局部抗肿瘤活性，但重要的是，还能促进全身性反应，从而限制远处肿瘤的生长。因此，这种治疗形式可用于临床上可触及转移性肿瘤病变的情况，或作为新辅助治疗。在这篇综述中，我们总结了目前关于肿瘤内注射PRR激动剂的临床前数据，包括优化给药和效果的新策略，以及与当前和有前景的新型癌症治疗方法的联合研究。
