Abstract
Immune checkpoints blockade (ICB) has made revolutionary progress in cancer therapy recently. The development of blocking agents to checkpoints on coinhibitory pathway, which prevents inflammation-induced tissue damage but also induces the cancer immune evasion, and retrieves the productive immune responses against tumors. The striking clinical trial results of ICB, by targeting the cytotoxic T lymphocyte–associated protein 4 (CTLA-4), the programmed cell death 1 (PD-1) or PD-1 ligand 1 (PD-L1), has promoted the approval of multiple antibodies for several cancer types by the US Food and Drug Administration (FDA). In addition, the combination of multiple types of blockade even increased the efficacy of tumor regression. Following the previous success, other immune checkpoints have also been verified, such as lymphocyte-activated gene-3 (LAG-3) and Signal-regulatory Protein alpha (SIRPα). However, not all patients can get benefits from ICB and the mechanisms of these coinhibitory pathways are not quite clear. Therefore, understanding the mechanisms of ICB is a formidable challenge that could have far reaching guidelines for therapeutic strategies in cancer. This article summarizes the literature to date regarding ICB that may help more patients get benefit from immunotherapy.
Highlights
Immune checkpoints like cytotoxic T lymphocyte– associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), lymphocyte-activated gene-3 (LAG-3), and SIRP-α are discovered to be used by tumor cells as tools to suppress the immune system
Immune checkpoints like CTLA-4, PD-1, LAG-3, and SIRP-α are discovered to be used by tumor cells as tools to suppress the immune system
CTLA-4 is a homolog of T-lymphocytes co-stimulatory receptor CD28, and they bind to the same ligands B71(CD80) and B7-2(CD86), but CTLA-4 has a higher affinity to those ligands.[1]
Summary
Immune checkpoints like CTLA-4, PD-1, LAG-3, and SIRP-α are discovered to be used by tumor cells as tools to suppress the immune system. Monoclonal antibodies were developed to block the signaling between those molecules and their ligands. Most of those Abs showed significant effect on the regression of the tumor cells on clinical trials and some of them were officially proved and created as commercials. We are going to introduce some of the immune checkpoints and their mechanisms, and present their functions as therapeutic targets
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