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Cancer Immunotherapy: Antigen Presentation
Tumor-associated antigens (TAA) can be internalized by receptors on antigen presenting cells such as dendritic cells (DC). They are processed into short peptides by a variety of proteases and then loaded onto MHC molecules for expression on the cell surface.
Classically, the presentation of extracellular-derived antigens involves MHC class II molecules and promotes CD4+ helper T cell activation and humoral immunity. The presentation of intracellular molecules (as with virus-infected cells) alternatively involves MHC class I molecules and promotes the activation of cytolytic CD8+ T cells.
In antigen cross-presentation, extracellular antigens are presented in complex with MHC class I instead of class II molecules. For cancer vaccines, DC are engineered so they present extracellularly-derived TAA with MHC class I molecules to generate cytolytic activity directed at the tumor cells. In vacuolar cross-presentation, antigen processing and loading onto MHC-I takes place in endocytic compartments. In cytosolic cross-presentation, antigens are processed by cytosolic proteasomes before loading onto MHC-I. Cross-presentation by dendritic cells is enhanced by GM-CSF and mediated by the C-type lectins DEC-205/CD205, MMR/CD206, DCIR/CLEC4A, DCIR2, and Siglec-H.