Collagen expression and structure in the tumour microenvironment are associated with tumour development and
therapy response. Leukocyte-associated
immunoglobulin-like receptor-1 (LAIR-1) is a widely expressed inhibitory
collagen receptor. LAIR-2 is a soluble homologue of LAIR-1 that competes for
collagen binding. Multiple studies in mice implicate blockade of LAIR-1:
collagen interaction in
cancer as a promising therapeutic strategy. Here, we investigated the role of LAIR-1 in anti-tumour responses. We show that although LAIR-1 inhibits activation, proliferation, and
cytokine production of mouse T cells in vitro, tumour outgrowth in LAIR-1-deficient mice did not differ from wild type mice in several in vivo tumour models. Furthermore, treatment with NC410, a LAIR-2-Fc fusion
protein, did not result in increased tumour clearance in tested immunocompetent mice, which contrasts with previous data in humanized mouse models. This discrepancy may be explained by our finding that NC410 blocks human LAIR-1:
collagen interaction more effectively than mouse LAIR-1:
collagen interaction. Despite the lack of therapeutic impact of NC410 monotherapy, mice treated with a combination of NC410 and anti-
programmed death-ligand 1 did show reduced tumour burden and increased survival. Using LAIR-1-deficient mice, we showed that this effect seemed to be dependent on the presence of LAIR-1. Taken together, our data demonstrate that the absence of LAIR-1 signalling alone is not sufficient to control tumour growth in multiple immunocompetent mouse models. However, combined targeting of LAIR-1 and PD-L1 results in increased tumour control. Thus, additional targeting of the LAIR-1:
collagen pathway with NC410 is a promising approach to treating tumours where conventional
immunotherapy is ineffective.