Investigating the function and therapeutic potential of a novel human myeloid checkpoint receptor, LILRB3 (ILT5)

Abstract

The human leukocyte immunoglobulin-like receptor (LILR) B3 belongs to the immune inhibitory subfamily of LILRs. LILRB3 contains four immunoreceptor tyrosine-based inhibitory motifs in its cytoplasmic domain, which recruit phosphatases to abrogate the propagation of activatory signalling cascades. Despite its discovery in the late 1990s, its function on myeloid cells and therapeutic potential has not been elucidated.

As LILRB3 is only expressed in humans, a transgenic (Tg) mouse was generated to investigate its function alongside human antibodies specific for the receptor. LILRB3 expression in the Tg mouse recapitulated that in healthy human blood and confirmed its restricted expression on myelomonocytic cells, while being absent on lymphocytes. Our studies revealed previously unknown immunoinhibitory functions of LILRB3 in myeloid cells and suggest its potential as a novel myeloid checkpoint inhibitor.

Having confirmed the expression and immunoinhibitory function of LILRB3 in humans and in the LILRB3 Tg mouse model, the therapeutic potential of the receptor as a target for immunotherapy for acute myeloid leukaemia (AML) was investigated. Collectively, our data demonstrated that LILRB3 is a viable target for AML immunotherapy, providing impetus to further explore this potential new therapy in vivo and in AML patients.

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Identifiers

ORCID for Ali Roghanian: orcid.org/0000-0003-1316-4218

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