Abstract
Immune checkpoints play important roles in immune regulation, and blocking immune checkpoints on the cell membrane is a promising strategy in the treatment of cancer. Based on this, monoclonal antibodies are having much rapid development, such as those against CTLA-4 (cytotoxic T lymphocyte antigen 4) and PD-1 (programmed cell death protein 1).But the cost of preparation of monoclonal antibodies is too high and the therapeutic effect is still under restrictions. Recently, a series of soluble immune checkpoints have been found such as sCTLA-4 (soluble CTLA-4) and sPD-1 (soluble PD-1). They are functional parts of membrane immune checkpoints produced in different ways and can be secreted by immune cells. Moreover, these soluble checkpoints can diffuse in the serum. Much evidence has demonstrated that these soluble checkpoints are involved in positive or negative immune regulation and that changes in their plasma levels affect the development, prognosis and treatment of cancer. Since they are endogenous molecules, they will not induce immunological rejection in human beings, which might make up for the deficiencies of monoclonal antibodies and enhance the utility value of these molecules. Therefore, there is an increasing need for investigating novel soluble checkpoints and their functions, and it is promising to develop relevant therapies in the future. In this review, we describe the production mechanisms and functions of various soluble immune checkpoint receptors and ligands and discuss their biological significance in regard to biomarkers, potential candidate drugs, therapeutic targets, and other topics.
Highlights
Immune checkpoints are molecules that can increase or decrease the signals of the immune system, and they are considered to be critical factors in treating infections, cancers and autoimmune diseases
Gu et al Journal for ImmunoTherapy of Cancer (2018) 6:132 example, alternative splice variants of the human PD-1 and Cytotoxic Tlymphocyte-associated protein 4 (CTLA-4) genes have been identified, and Soluble PD-1 (sPD-1) can interfere with Programmed cell death ligand-1/2 (PD-L1/2):full-length PD-1 interactions, thereby blocking the negative signal imparted by the transmembrane form of PD-1 [4, 5]
Several studies have documented many types of soluble receptors and ligands that can be detected in the plasma in cancer, and the plasma levels are related to the severity of cancer
Summary
Immune checkpoints are molecules that can increase or decrease the signals of the immune system, and they are considered to be critical factors in treating infections, cancers and autoimmune diseases. CTLA-4 is considered to be the first functional immune checkpoint, as it stops T cells in lymph nodes at the. Gu et al Journal for ImmunoTherapy of Cancer (2018) 6:132 example, alternative splice variants of the human PD-1 and CTLA-4 genes have been identified, and sPD-1 can interfere with PD-L1/2 (programmed cell death ligand-1/ 2, known as B7-H1/2):full-length PD-1 interactions, thereby blocking the negative signal imparted by the transmembrane form of PD-1 [4, 5]. Several studies have documented many types of soluble receptors and ligands that can be detected in the plasma in cancer, and the plasma levels are related to the severity of cancer. Since previous studies suggested that soluble receptors and ligands should be considered therapeutic targets in cancer, we introduce some common therapeutic targets. We conclude the use of immunotherapy based on these soluble molecules
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