Single-cell RNA-sequencing of myeloid cells in E0771 breast tumours from CD1d-KO and WT mice

Myeloid cells play crucial roles in cancer progression, influencing tumour growth, metastasis, and response to immunotherapy. Tumour-infiltrating myeloid cells are highly heterogeneous, with functions ranging from anti-tumour to tumour-promoting. The mechanisms shaping these populations remain poorly understood and may offer therapeutic opportunities. Here, we identified the lipid-presenting molecule CD1d as a regulator of tumour progression and myeloid heterogeneity in the tumour microenvironment. CD1d-deficient mice exhibit reduced tumour growth and altered immune-infiltrates in breast cancer models. Similarly, targeting CD1d with an antibody, suppresses tumour growth, reshapes the myeloid landscape, and improves anti-PD-1 immunotherapy efficacy. The CD1d-dependent control of myeloid cell functional differentiation is cell-intrinsic and conserved in human and mouse. Single-cell RNA-sequencing revealed an enhanced proinflammatory program and accumulation of inflammatory monocytes in tumours from CD1d-KO animals. Subsequently, we generated a CD1d-KO-associated gene signature that predicts clinical outcomes and response to immunotherapy in breast cancer patients. Thus, CD1d could be targeted to alter tumour-infiltrating myeloid populations and enhance immunotherapy responses.