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.

MATERIAL AND 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: Xiaodong Li, Wenwei Hu, Xiao Zheng, Chu Zhang, Peng Du, Zhuojun Zheng, Yan Yang, Jun Wu, Mei Ji, Jingting Jiang, Changping Wu
• Journal: Acta oncologica (Stockholm, Sweden) (Acta Oncol) Vol. 54 Issue 10 Pg. 1706-13 (Nov 2015) ISSN: 1651-226X [Electronic] England
• PMID: 26361073 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antigens, CD
• HAVCR2 protein, human
• Hepatitis A Virus Cellular Receptor 2
• Membrane Proteins
• Lymphocyte Activation Gene 3 Protein
• Lag3 protein, human
• soluble LAG-3 protein, human

Topics

• Antigens, CD (immunology, metabolism, therapeutic use)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Hepatitis A Virus Cellular Receptor 2
• Humans
• Immunotherapy (methods)
• Membrane Proteins (antagonists & inhibitors, immunology, metabolism)
• Neoplasms (therapy)
• Th1 Cells (immunology)
• Tumor Microenvironment (immunology)
• Lymphocyte Activation Gene 3 Protein