Cancer immunotherapy based on blocking immune suppression mediated by an immune modulator LAIR-1

• Published in: Oncoimmunology Vol. 9; no. 1; p. 1740477
• Main Authors: Xu, Lijun, Wang, Shanlong, Li, Jufeng, Li, Jie, Li, Bingyu
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.01.2020; Taylor & Francis Group
• Subjects: Back Matter; collagen; inhibitory immune receptor; ITIM; LAIR-1; LAIR-2; collagen; inhibitory immune receptor; LAIR-1; LAIR-2; ITIM
• ISSN: 2162-402X; 2162-4011; 2162-402X
• DOI: 10.1080/2162402X.2020.1740477

The leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1) is an inhibitory receptor expressed on the majority of peripheral blood mononuclear cells and is important for the regulation of immune responses. The binding of LAIR-1 to its ligands results in the loss of immune function in the tumor microenvironment (TME) and a reduction in T cell function and immune responses of antigen-presenting cells. Using bioinformatics analysis, we showed that LAIR-1 is broadly upregulated in multiple types of cancer. By designing a LAIR-2-Fc recombinant protein to block the binding of LAIR-1 to its ligand collagen, we observed augmented cytotoxic T cell infiltration and function resulting in antitumor immune responses that eliminated cancer cells. Besides, LAIR-2-Fc fusion protein potentiated the antitumor effect of PD-1/L1 checkpoint blockade therapy. Collectively, our results support the targeting of LAIR-1 for potential immunotherapeutic applications.