Journal
CANCER LETTERS
Volume 510, Issue -, Pages 67-78Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2021.04.011
Keywords
TIM3; Gal9; Immuno-oncology; Immune checkpoint receptors; Immune checkpoint blockade; Immune suppression
Categories
Funding
- National Institutes of Health, United States [R01CA231099, R01AA021510]
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The blockade of the TIM3/Gal9 pathway shows promising therapeutic potential in cancer treatment, by enhancing immune response and overcoming immune resistance. TIM3 and Gal9 may also serve as prognostic and predictive biomarkers in different types of cancers.
Immune checkpoint blockade has shown unprecedented and durable clinical response in a wide range of cancers. T cell immunoglobulin and mucin domain 3 (TIM3) is an inhibitory checkpoint protein that is highly expressed in tumor-infiltrating lymphocytes. In various cancers, the interaction of TIM3 and Galectin 9 (Gal9) suppresses antitumor immunity mediated by innate as well as adaptive immune cells. Thus, the blockade of the TIM3/Gal9 interaction is a promising therapeutic approach for cancer therapy. In addition, co-blockade of the TIM3/Gal9 pathway along with the PD-1/PD-L1 pathway increases the therapeutic efficacy by overcoming non-redundant immune resistance induced by each checkpoint. Here, we summarize the physiological roles of the TIM3/Gal9 pathway in adaptive and innate immune systems. We highlight the recent clinical and preclinical studies showing the involvement of the TIM3/Gal9 pathway in various solid and blood cancers. In addition, we discuss the potential of using TIM3 and Gal9 as prognostic and predictive biomarkers in different cancers. An in-depth mechanistic understanding of the blockade of the TIM3/Gal9 signaling pathway in cancer could help in identifying patients who respond to this therapy as well as designing combination therapies.
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