Cross-presentation by the others

The critical role of conventional dendritic cells in physiological cross-priming of immune responses to tumors and pathogens is widely documented and beyond doubt. However, there is ample evidence that a wide range of other cell types can also acquire the capacity to cross-present. These include not only other myeloid cells such as plasmacytoid dendritic cells, macrophages and neutrophils, but also lymphoid populations, endothelial and epithelial cells and stromal cells including fibroblasts. The aim of this review is to provide an overview of the relevant literature that analyzes each report cited for the antigens and readouts used, mechanistic insight and in vivo experimentation addressing physiological relevance. As this analysis shows, many reports rely on the exceptionally sensitive recognition of an ovalbumin peptide by a transgenic T cell receptor, with results that therefore cannot always be extrapolated to physiological settings. Mechanistic studies remain basic in most cases but reveal that the cytosolic pathway is dominant across many cell types, while vacuolar processing is most encountered in macrophages. Studies addressing physiological relevance rigorously remain exceptional but suggest that cross-presentation by non-dendritic cells may have significant impact in anti-tumor immunity and autoimmunity.

Automated summary

The critical role of conventional dendritic cells in the immune response to tumors and pathogens is well-established. However, various other cell types, including myeloid, lymphoid, endothelial, epithelial, and stromal cells, have been shown to also possess the ability to cross-present antigens. This review analyzes the literature on this topic, discussing the antigens and readouts used, mechanistic insights, and in vivo experimentation. While many studies rely on artificial systems, there is evidence to suggest that cross-presentation by non-dendritic cells may have significant implications in anti-tumor immunity and autoimmunity.