Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4

• Published in: Molecular cancer Vol. 18; no. 1; p. 155
• Main Authors: Qin, Shuang, Xu, Linping, Yi, Ming, Yu, Shengnan, Wu, Kongming, Luo, Suxia
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 06-11-2019; BioMed Central; BMC
• Subjects: Animals; Antibodies; Antigens; Antineoplastic Agents, Immunological - pharmacology; Antineoplastic Agents, Immunological - therapeutic use; Apoptosis; B cells; Biochemistry; Biomarkers, Tumor; Cancer; Cell death; Clinical trials; Clinical Trials as Topic; CTLA-4 Antigen - antagonists & inhibitors; Genes; Genetic research; Health aspects; Humans; Immune checkpoint; Immunoglobulins; Immunomodulation - drug effects; Immunotherapy; Ipilimumab; LAG-3; Lymphocyte Activation - drug effects; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Lymphocytes; Medical research; Molecular Targeted Therapy; Monoclonal antibodies; Neoplasms - drug therapy; Neoplasms - etiology; Neoplasms - metabolism; Neoplasms - pathology; Pembrolizumab; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Review; T cells; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; TIGIT; TIM-3; Treatment Outcome; Tumors; VISTA; Immune checkpoint; VISTA; LAG-3; Immunotherapy; B7-H3; BTLA; TIGIT; TIM-3
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/s12943-019-1091-2

The emergence of immune checkpoint inhibitors (ICIs), mainly including anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) and anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) monoclonal antibodies (mAbs), has shaped therapeutic landscape of some type of cancers. Despite some ICIs have manifested compelling clinical effectiveness in certain tumor types, the majority of patients still showed de novo or adaptive resistance. At present, the overall efficiency of immune checkpoint therapy remains unsatisfactory. Exploring additional immune checkpoint molecules is a hot research topic. Recent studies have identified several new immune checkpoint targets, like lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), T cell immunoglobulin and ITIM domain (TIGIT), V-domain Ig suppressor of T cell activation (VISTA), and so on. The investigations about these molecules have generated promising results in preclinical studies and/or clinical trials. In this review, we discussed the structure and expression of these newly-characterized immune checkpoints molecules, presented the current progress and understanding of them. Moreover, we summarized the clinical data pertinent to these recent immune checkpoint molecules as well as their application prospects.