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

Abstract

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.

• Authors: Lijun Xu, Shanlong Wang, Jufeng Li, Jie Li, Bingyu Li
• Journal: Oncoimmunology (Oncoimmunology) Vol. 9 Issue 1 Pg. 1740477 (04 07 2020) ISSN: 2162-402X [Electronic] United States
• PMID: 33457088 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.

Chemical References

• Ligands
• Collagen

Topics

• Collagen
• Immunotherapy
• Leukocytes, Mononuclear
• Ligands
• Neoplasms (drug therapy)
• Tumor Microenvironment