RE: Ruck14 May 2020 08:40
Antigen cross-presentation, the process in which exogenous antigens are presented on MHC class I molecules, is crucial for the generation of effector CD8+ T cell responses. Although multiple cell types are being described to be able to cross-present antigens, in vivo this task is mainly carried out by certain subsets of dendritic cells (DCs). Aspects such as the internalization route, the pathway of endocytic trafficking, and the simultaneous activation through pattern-recognition receptors have a determining influence in how antigens are handled for cross-presentation by DCs. In this review, we will summarize new insights in factors that affect antigen cross-presentation of human DC subsets, and we will discuss the possibilities to exploit antigen cross-presentation for immunotherapy against cancer.
Keywords: cross-presentation, dendritic cells, antigen processing and presentation, anti-cancer vaccine, CD8+ T cells
Scancell Immunobody achieves Cross Presentation in Patients ..............
mplications for Therapy Design – Future Directions
Our understanding in the mechanism of cross-presentation is crucial in the design of vaccination strategies aimed to induce protective immunity in the field of infectious diseases and cancer, which depends on the induction of both effector CD4+ and CD8+ T cells. Enhanced immune protection was obtained by long synthetic peptides compared to short peptides, which required cross-presentation of DC, resulting in long-lasting T cell stimulation that leads to the eradication of tumors (93, 94). Studies on improving cross-presentation-based vaccinations have emerged as a promising tool for immune intervention, based on many human in vitro studies and murine in vivo work. Strong focus on DC-targeting receptors in vivo that mediate endocytosis show potential of efficient induction of CD8+ T cell cross-priming, but can also lead to CD8+ T cell cross-tolerance. This fine tuning between the induction of immunity or tolerance is dictated by the various parameters that affect cross-presentation as mentioned under the Sections “Human DC Subsets and Antigen Cross-Presentation and Factors Determining Cross-Presentation,” the vaccine formulation, DC subset, receptor-targeting, endocytosis, and maturation stimuli. Many in vivo DC-targeting studies have been performed in mice that have demonstrated effective induction of tumor CD8+ effector T cell responses through targeting of CLRs, such as CD205, MR, CD207 (Langerin), CD209 (DC-SIGN), CLEC9A or other cell-surface receptors like integrins, HSP receptors, and glycolipids. In contrast, only a few of these DC-targeting vaccines have been tested in human clinical trails. Easy translation from mouse models to humans is complicated by the different expression levels of DC-targeting receptors and DC restriction and usage of TLRs between mouse and human. Moreover, still little is known on the cross-presenting capacity of human DC in situ. This has hampered the development of no
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