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Killer T cells can only attack a cancer once they have been shown pieces of it. A rare kind of immune cell, the type 1 dendritic cell, picks up debris from dead tumour cells and displays it in the special way killer T cells recognise. Without these cells, checkpoint drugs and many cancer vaccines work poorly in animal studies.
Most cells display on MHC class I only peptides from proteins they make themselves, so a CD8 T cell is normally primed by an infected or transformed cell's own antigen. Cross-presentation is the route by which certain dendritic cells take up exogenous antigen (from dead cells or debris), move it from the phagosome into the cytosolic processing pathway and load it onto MHC class I, priming CD8 T cells against antigens they did not synthesise. The subset specialised for this is the type 1 conventional dendritic cell (cDC1): CD8alpha+ and CD103+ in mice, CD141 (BDCA-3)+ in humans, dependent on FLT3 ligand and the transcription factor BATF3 for development, internalising necrotic-cell material through CLEC9A (DNGR-1), a receptor for polymerised actin, and expressing the chemokine receptor XCR1, which favours contact with CD8 T cells (Alfaro et al., 2013).
The in vivo proof came from Batf3-deficient mice (Hildner et al., Science 2008): they lacked CD8alpha+ dendritic cells, their dendritic cells were defective in cross-presentation, and they failed to reject highly immunogenic syngeneic tumours. In mouse melanoma, CD103+ dendritic cells were the only antigen-presenting cells carrying intact antigen to lymph nodes and priming tumour-specific CD8 T cells, and they were required for PD-L1 blockade to work; expanding them with FLT3 ligand and activating them with intratumoral poly I:C improved responses to PD-L1 and BRAF inhibition (Salmon et al., Immunity 2016). This is why a scarcity of cDC1 in a tumour is read as one cause of a cold, checkpoint-resistant tumour, and why vaccine designs target antigen to cDC1 receptors such as CLEC9A, or expand and activate these cells, rather than relying on bulk monocyte-derived dendritic cells.
In plain words · CD141 marks the rare dendritic cells that are best at showing tumour material to killer T cells. The same protein, under its other name thrombomodulin, is part of how blood clotting is kept in check.
Showing the target this term concerns: CD141.
Shares CD8, Hot vs cold tumours.
Shares Neoantigen, Hot vs cold tumours, PD-L1, Immune checkpoint inhibitors.
Shares Immune checkpoint, Antigen presentation & immune editing, Hot vs cold tumours, PD-L1.
Shares Immunogenic cell death, cGAS-STING innate sensing, Immune checkpoint inhibitors.
Shares Immunogenic cell death, Hot vs cold tumours, Immune checkpoint inhibitors.
Shares Neoantigen, Hot vs cold tumours, PD-L1, Immune checkpoint inhibitors.
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