2019 | Shuang Qin, Linping Xu, Ming Yi, Shengnan Yu, Kongming Wu and Suxia Luo
The emergence of immune checkpoint inhibitors (ICIs), primarily 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 significantly advanced the therapeutic landscape for certain cancers. Despite the compelling clinical effectiveness of some ICIs in specific tumor types, most patients still exhibit de novo or adaptive resistance. The overall efficiency of immune checkpoint therapy remains suboptimal. Exploring additional immune checkpoint molecules is a hot research topic. Recent studies have identified several new immune checkpoint targets, including 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 others. Preclinical studies and clinical trials have shown promising results for these new targets. This review discusses the structure and expression of these newly-characterized immune checkpoint molecules, presents the current progress and understanding of them, and summarizes the clinical data pertinent to these recent immune checkpoint molecules, highlighting their potential application prospects.The emergence of immune checkpoint inhibitors (ICIs), primarily 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 significantly advanced the therapeutic landscape for certain cancers. Despite the compelling clinical effectiveness of some ICIs in specific tumor types, most patients still exhibit de novo or adaptive resistance. The overall efficiency of immune checkpoint therapy remains suboptimal. Exploring additional immune checkpoint molecules is a hot research topic. Recent studies have identified several new immune checkpoint targets, including 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 others. Preclinical studies and clinical trials have shown promising results for these new targets. This review discusses the structure and expression of these newly-characterized immune checkpoint molecules, presents the current progress and understanding of them, and summarizes the clinical data pertinent to these recent immune checkpoint molecules, highlighting their potential application prospects.