Table 2.
Expression pattern of soluble isoform of immune checkpoints (ICs) and their effects on tumor microenvironment.
| Immune Checkpoint | Cellular Expression | Ligand | Cellular Expression | Effects in Tumor Microenvironment | Ref. |
|---|---|---|---|---|---|
| sCTLA-4 | Monocytes, immature DCs, and Treg cells | CD80, CD86 | APCs | Inhibits T cell responses | [56] |
| sPD-1 | PBMCs | PD-L1/2 | Tumor cells | Blocks PD-L/PD-1 interactions, Activates CD8+ T cells |
[57] |
| sPD-L1 | Mature DCs | PD-1 | T cells | Combines with PD-1, inhibits T cell responses, and reduces T cell proliferation | [58,59] |
| sPD-L2 | Activated leukocytes | PD-1 | - | Unknown function | [60] |
| sCD80 (sB7–1) | unstimulated B cells and monocytes, and activated T and B cells | CTLA-4, CD28 | T cells | Inhibits PD-1/PD-L1 pathway, T cell proliferation, and IL-2 production | [61] |
| sCD86 (sB7–2) | Constitutively expressed on APCs, monocytes, DC, and certain cancer cells | CTLA-4, CD28 | T cells | Inhibits T cell responses | [61] |
| sB7-H3 | Monocytes, DCs, and activated T cells | B7-H3R | T cells | Promotes IL-8 and VEGF expression, increasing invasion and metastases of pancreatic carcinoma cells | [62,63] |
| sCD137 (s4-1BB) | Activated PBMCs | CD137L (4-1BBL) |
T cells | Inhibits CD137/CD137L pathway | [64] |
APC: antigen-presenting cell; DC: dendritic cell; PMBCs: peripheral blood mononuclear cells; Tregs: regulatory T cells.