Progress on tumor immune checkpoints and their inhibitors in tumor therapy

The discovery of tumor immune checkpoints provides a new idea for tumor immunotherapy. New immune checkpoints such as T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), lymphocyte activation gene-3 (LAG-3/CD223), T cell immunoglobulin and ITIM domain (TIGIT), B and T lymphocyte attenuator (BTLA) and V-domain Ig-containing suppressor of T cell activation (VISTA) have also been gradually found besides the traditional immune checkpoints cytotoxic T-lymphocyte-associated protein-4 (CTLA4) and programmed death 1 (PD-1), which greatly enriches the choice of tumor immunotherapy. Related immune checkpoint inhibitors including CTLA4 inhibitors such as ipilimumab and tremelimumab, PD-1/programmed death 1 ligand 1 (PD-L1) inhibitors such as nivolumab, pembrolizumab and atezolizumab have been prepared and applied in the therapy of solid tumors such as melanoma, non-small cell lung cancer, digestive tract tumors and so on, which have get a huge success. However, immune-related adverse events and drug resistance should also be paid enough attention. This review mainly focuses on tumor immune checkpoints, immune checkpoint inhibitors and their application in the treatment of malignant tumors.