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Review
. 2015 Nov;54(10):1706-13.
doi: 10.3109/0284186X.2015.1071918. Epub 2015 Sep 11.

Emerging immune checkpoints for cancer therapy

Xiaodong Li  1   2   3 , Wenwei Hu  1   2   3 , Xiao Zheng  2   3 , Chu Zhang  1 , Peng Du  2   3 , Zhuojun Zheng  4 , Yan Yang  1 , Jun Wu  1 , Mei Ji  1 , Jingting Jiang  2   3 , Changping Wu  1   2   3
Affiliations
Review

Emerging immune checkpoints for cancer therapy

Xiaodong Li et al. Acta Oncol. 2015 Nov.

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.

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