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Table 1 Basic information about the soluble receptors and ligands

From: Soluble immune checkpoints in cancer: production, function and biological significance

Soluble receptors/ligands Structure Cell source Production Ligands/receptors Main functions references
sPD-1 Monomer PBMCs (peripheral blood mononuclear cells) mRNA expression PD-L1/2 1. Block PD-L/PD-1 interactions
2. Activate CD8+ T cells
[4, 19, 20, 23, 24]
sPD-L1 Unknown Mature DCs Possible cleavage of membrane-bound proteins PD-1 1. Combine with PD-1
2. Inhibit T-cell responses
[31, 32, 44]
sPD-L2 Unknown Activated leukocytes mRNA expression PD-1 Unknown [45]
sCTLA-4 Monomer Monocytes/immature DCs/Treg cells mRNA expression CD80/CD86 Inhibit T-cell responses [46, 47, 51, 52]
sCD80 (sB7–1) Homodimer Unstimulated monocytes/B cells mRNA expression CTLA-4 /CD28 Inhibit PD-1/PD-L1 pathway [53, 54, 56, 59, 60]
sCD86 (sB7–2) Monomer Resting monocytes/DCs Cleavage of membrane-bound proteins/mRNA expression CTLA-4 Inhibit T-cell responses [65, 69]
sB7-H3 Unknown Monocytes/ DCs/activated T cells Cleavage of membrane-bound proteins/mRNA expression B7-H3R Promote IL-8 and VEGF expression [70, 71, 77]
sCD137 (s4-1BB) Unknown Activated PBMCs Cleavage of membrane-bound proteins/mRNA expression CD137L Inhibit CD137/CD137L pathway [78, 79, 82]
  1. For example, sPD-1 has been reported to be a monomer, and it can be produced by PBMCs through mRNA expression. Moreover, sPD-1 can combine with PD-L1 and PD-L2, thus blocking PD-L/PD-1 interactions and somehow activating CD8+ T cells. Some soluble receptors can be produced by the cleavage of membrane-bound proteins or by both the cleavage of membrane-bound proteins and mRNA expression