생화학분자생물학회

	Name: Yoon Park ( ypark@kist.re.kr )
	2018-present	Senior member, Department of Molecular Biotechnology, Korea Institute of Science and Technology
	2016-2018	Senior Research Investigator, Bristol-Myers Squibb, USA
	2015-2016	Senior Scientist, Pfizer Inc, USA
	2009-2015	Postdoctoral research fellow/Instructor, La Jolla Institute for Immunology, USA
	2004-2008	Ph.D., Department of Biochemistry, Yonsei University, Korea

Hitting the complexity of the TIGIT-CD96-CD112R-CD226 axis for next-generation cancer immunotherapy

Antibody-based therapeutics targeting the inhibitory receptors PD-1, PD-L1, or CTLA-4 have shown remarkable clinical progress in several cancers. However, the majority of patients do not benefit from these therapies. Thus, there are many efforts to identify new immune checkpoint receptor-ligand pathways that represent alternative targets for cancer immunotherapies. Nectin and nectin-like molecules are widely expressed on several types of tumor cells and play regulatory roles in T and NK cell functions. TIGIT, a co-inhibitory receptor that interacts with CD155 (PVR), CD112 (Nectin-2), CD113 (Nectin-3), and Nectin-4 (PVRL4), is an immune checkpoint in T and NK cell activation. TIGIT shares ligands with CD226 (DNAM-1), CD96 (TACTILE), and CD112R (PVRIG). The integrated signals formed by the complex interaction between nectin and nectin-like molecules and their cognate receptors contributes to regulate immune cell functions. Several clinical trials are currently evaluating the efficacy of anti-TIGIT and anti-CD112R blockade for treating patients with solid tumors. However, many questions remain to be answered to fully understand the dynamics and functions of these receptor networks. This review addresses the rationale behind targeting TIGIT, CD226, CD96, and CD112R to regulate T and NK cell functions, and discusses their potential application in cancer immunotherapy.


BMB Rep 2020 Dec 11;5207. Online ahead of print. https://pubmed.ncbi.nlm.nih.gov/33298247/