Exciting progress of cancer immunotherapy focusing on immune checkpoints

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 (SIRP alpha). 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.