Recent Progress in Dendritic Cell-Based Cancer Immunotherapy

SIMPLE SUMMARY: Cancer immunotherapy has now attracted much attention because of the recent success of immune checkpoint inhibitors. However, they are only beneficial in a limited fraction of patients most probably due to lack of sufficient CD8+ cytotoxic T-lymphocytes against tumor antigens in the host. In this regard, dendritic cells are useful tools to induce host immune responses against exogenous antigens. In particular, recently characterized cross-presenting dendritic cells are capable of inducing CD8+ cytotoxic T-lymphocytes against exogenous antigens such as tumor antigens and uniquely express the chemokine receptor XCR1. Here we focus on the recent progress in DC-based cancer vaccines and especially the use of the XCR1 and its ligand XCL1 axis for the targeted delivery of cancer vaccines to cross-presenting dendritic cells. ABSTRACT: Cancer immunotherapy aims to treat cancer by enhancing cancer-specific host immune responses. Recently, cancer immunotherapy has been attracting much attention because of the successful clinical application of immune checkpoint inhibitors targeting the CTLA-4 and PD-1/PD-L1 pathways. However, although highly effective in some patients, immune checkpoint inhibitors are beneficial only in a limited fraction of patients, possibly because of the lack of enough cancer-specific immune cells, especially CD8(+) cytotoxic T-lymphocytes (CTLs), in the host. On the other hand, studies on cancer vaccines, especially DC-based ones, have made significant progress in recent years. In particular, the identification and characterization of cross-presenting DCs have greatly advanced the strategy for the development of effective DC-based vaccines. In this review, we first summarize the surface markers and functional properties of the five major DC subsets. We then describe new approaches to induce antigen-specific CTLs by targeted delivery of antigens to cross-presenting DCs. In this context, the chemokine receptor XCR1 and its ligand XCL1, being selectively expressed by cross-presenting DCs and mainly produced by activated CD8(+) T cells, respectively, provide highly promising molecular tools for this purpose. In the near future, CTL-inducing DC-based cancer vaccines may provide a new breakthrough in cancer immunotherapy alone or in combination with immune checkpoint inhibitors.