title: Emerging immune checkpoints for cancer therapy.
abstract: BACKGROUND
  Immunotherapy with immune checkpoint inhibitors has emerged as promising treatment modality for cancer based on the success of anti-CTLA-4 and -PD-1/PD-L1 antibodies. LAG-3 and TIM-3 are two new immune checkpoints. The aim of this work is to review the role and application of LAG-3 and TIM-3 for cancer immunotherapy.
  
  
  METHODS
  Literatures were searched and collected in Medline/PubMed.
  
  
  RESULTS
  LAG-3 is presented as a CD4 homolog type I transmembrane protein which binds MHC class II molecules. LAG-3 negatively regulates T cell proliferation, homeostasis and function. IMP321 is formed of an extracellular portion of human LAG-3 fused to the Fc fraction of human IgG1 and has shown increased T cell responses and tolerability in phase I studies on advanced renal cell cancer. When combined with paclitaxel, IMP321 has exerted immune enhancement and tumor inhibition with no significant IMP321-related adverse events. TIM-3 belongs to the TIM family and mainly negatively regulates Th1 immunity. The TIM-3/galectin-9 pathway contributes to the suppressive tumor microenvironment. TIM-3 overexpression is associated with poor prognosis in a variety of cancers. Both LAG-3 and TIM-3 are coexpressed with other immune checkpoints. The application of LAG-3 or TIM-3 does play an important role in anti-tumor responses, and maybe better when combing with anti-CTLA-4 and anti-PD-1/L1 antibodies.
  
  
  CONCLUSIONS
  These two immune checkpoints play crucial roles in cancer development and may be used in future clinical practice of cancer therapy.
authors.affiliation: a Department of Oncology , The Third Affiliated Hospital of Soochow University , Changzhou , China.|b Department of Tumor Biological Treatment , The Third Affiliated Hospital of Soochow University , Changzhou , China.|c Jiangsu Engineering Research Center for Tumor Immunotherapy , Changzhou , China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.affiliation: a Department of Oncology , The Third Affiliated Hospital of Soochow University , Changzhou , China.|b Department of Tumor Biological Treatment , The Third Affiliated Hospital of Soochow University , Changzhou , China.|c Jiangsu Engineering Research Center for Tumor Immunotherapy , Changzhou , China.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Hu
authors.affiliation: b Department of Tumor Biological Treatment , The Third Affiliated Hospital of Soochow University , Changzhou , China.|c Jiangsu Engineering Research Center for Tumor Immunotherapy , Changzhou , China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zheng
authors.affiliation: a Department of Oncology , The Third Affiliated Hospital of Soochow University , Changzhou , China.
authors.forename: Chu
authors.initials: C
authors.lastname: Zhang
authors.affiliation: b Department of Tumor Biological Treatment , The Third Affiliated Hospital of Soochow University , Changzhou , China.|c Jiangsu Engineering Research Center for Tumor Immunotherapy , Changzhou , China.
authors.forename: Peng
authors.initials: P
authors.lastname: Du
authors.affiliation: d Department of Hematology , The Third Affiliated Hospital of Soochow University , Changzhou , China.
authors.forename: Zhuojun
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: a Department of Oncology , The Third Affiliated Hospital of Soochow University , Changzhou , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: a Department of Oncology , The Third Affiliated Hospital of Soochow University , Changzhou , China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: a Department of Oncology , The Third Affiliated Hospital of Soochow University , Changzhou , China.
authors.forename: Mei
authors.initials: M
authors.lastname: Ji
authors.affiliation: b Department of Tumor Biological Treatment , The Third Affiliated Hospital of Soochow University , Changzhou , China.|c Jiangsu Engineering Research Center for Tumor Immunotherapy , Changzhou , China.
authors.forename: Jingting
authors.initials: J
authors.lastname: Jiang
authors.affiliation: a Department of Oncology , The Third Affiliated Hospital of Soochow University , Changzhou , China.|b Department of Tumor Biological Treatment , The Third Affiliated Hospital of Soochow University , Changzhou , China.|c Jiangsu Engineering Research Center for Tumor Immunotherapy , Changzhou , China.
authors.forename: Changping
authors.initials: C
authors.lastname: Wu
mesh_terms: D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism; D009369:Neoplasms / Q000628:therapy*; D018417:Th1 Cells / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; D000093322:Lymphocyte Activation Gene 3 Protein; C000720326:Lag3 protein, human; C000720328:soluble LAG-3 protein, human