Modulating the Tumour Microenvironment by Intratumoural Injection of Pattern Recognition Receptor Agonists

SIMPLE SUMMARY: The immune system is capable of eliminating solid cancers through the action of immune cells that recognise antigens that are unique to tumour tissue. However, the activity of tumour-specific immune cells is often blunted by the immunosuppressive environment within the tumour core. One strategy to overcome this limitation is to inject immune modulators directly into the tumour bed to stimulate the local network of immune cells. Not only does this promote local antitumour activity, but also facilitates the infiltration of immune cells with antitumour activity at distant tumour sites. A major class of compounds used for this purpose are recognised by pattern recognition receptors (PRR), providing molecular cues typically associated with infection or tissue damage to inflate the response. In this review, we summarise research into the use of such compounds in preclinical studies, including promising studies conducted in combination with conventional cancer therapies and other immunotherapies. ABSTRACT: 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.