Abstract
The use of dendritic cells (DCs) to generate effective anti-tumor T cell immunity has garnered much attention over the last thirty-plus years. Despite this, limited clinical benefit has been demonstrated thus far. There has been a revival of interest in DC-based treatment strategies following the remarkable patient responses observed with novel checkpoint blockade therapies, due to the potential for synergistic treatment. Cross-presenting DCs are recognized for their ability to prime CD8+ T cell responses to directly induce tumor death. Consequently, they are an attractive target for next-generation DC-based strategies. In this review, we define the universal classification system for cross-presenting DCs, and the vital role of this subset in mediating anti-tumor immunity. Furthermore, we will detail methods of targeting these DCs both ex vivo and in vivo to boost their function and drive effective anti-tumor responses.
Highlights
The revolutionary success of cancer immunotherapies harnessing T cell immunity has renewed interest in novel therapeutic strategies targeting dendritic cells (DCs)
The majority of patients receiving immune checkpoint blockade therapy (ICB) succumb to their disease, with therapy failure partially attributed to insufficient recruitment of tumor-specific T cells [2]
There have been over 200 clinical trials evaluating the use of DC vaccines against cancer, whereby DCs are loaded ex vivo with cancer-derived antigens to induce T cell immunity [4,5]
Summary
The revolutionary success of cancer immunotherapies harnessing T cell immunity has renewed interest in novel therapeutic strategies targeting dendritic cells (DCs). The majority of patients receiving ICB succumb to their disease, with therapy failure partially attributed to insufficient recruitment of tumor-specific T cells [2] This highlights the need for effective vaccines targeting the generation of robust T cell immunity capable of synergizing with established treatments. Since their discovery in 1973 [3], DCs have been recognized for their unique ability to link the innate and adaptive arms of the immune system via presentation of antigen to T cells. They have long been considered attractive targets for anti-cancer therapies. We will discuss the defining features of the cross-presenting DC population, methods of targeting them for the generation of effective CD8+ T cell-driven anti-tumor responses, and the potential for these approaches to synergize with ICB
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