Targeting Toll-like receptor 3 in dendritic cells for cancer immunotherapy

Activation of innate immune system is a key step to develop anti-tumor immunity. Antigen-presenting dendritic cells (DCs) cross-present tumor-associated antigens to cytotoxic CD8⁺ T cells (CTLs). Signaling from pattern-recognition receptors (PRRs) in DCs is required to induce tumor-specific CTLs.

This review summarizes the properties of PRRs expressed by antigen-presenting DCs, especially TLR3, and provides the recent knowledge of their function in anti-tumor immunity. We also summarize the characteristics of newly-developed TLR3-specific agonist, ARNAX, which efficiently primes DCs to induce anti-tumor immunity without systemic inflammation in mice.

In cancer immunotherapy, the induction of tumor-specific CTLs is significant for tumor regression and to augment the efficacy of PD-1/PD-L1 blockade. Non-inflammatory TLR3 adjuvant ARNAX that can induce tumor-specific CTLs without inducing inflammation benefits cancer immunotherapy. Development of appropriate protocols for ARNAX vaccine therapy would be useful to overcome the PD-1/PD-L1 blockade resistance.