Multiomics immune profiling of a patient-relevant orthotopic lung cancer model using SEPARATE-Seq
(2026) Nature Communications — Vol. /, p. / (2026)
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Bardet, Pauline M. R. 
Allonsius, Lize Kancheva, Daliya - et. al.
- Abstract
- (en) Relevant pre-clinical models are essential for driving progress in cancer therapy research. Here, we develop a pre-clinical study framework using an injectable orthotopic lung adenocarcinoma (LUAD) model (ORTHO) that replicates key features of human LUAD patients and is dissectible into tumoural and non-tumoural adjacent tissue, in analogy with patient samples. We also present SEPARATE-Seq, a broadly applicable technique enabling the partitioning of vascular and intratissue immune cells along with scRNA-Seq. By applying both SEPARATE-Seq and spatial transcriptomics to our dissectible ORTHO model, we confirm that our model replicates key immune features of human LUAD patients. Similarly to these patients, we observe NK-cell dysfunction and neutrophil dichotomy, and show that these are affected by their vascular/intratissue or tumour/adjacent location, highlighting the need for these spatial distinctions. Additionally, we show that several immune populations are restricted to specialised, local niches within the tumour, including a ring of lipid-associated TAMs lining the tumour edge and hubs of interferon-stimulated cells. Overall, our resource, available through an interactive tool, provides a comprehensive multiomics immune characterisation of a reproducible pre-clinical LUAD mouse model.
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Citations
Bardet, P. M. R., Allonsius, L., Hadadi, E., Kancheva, D., Paque, M., Vosahlikova, S., Caro, A. A., Van Audenhove, A., Debraekeleer, A., Roelandt, R., Verstaen, K., Hensler, M., Hoton, D., Mateu Cabrera, G., Boon, L., Blomme, A., Deschoemaeker, S., Raes, G., Marcq, E., et al. (2026). Multiomics immune profiling of a patient-relevant orthotopic lung cancer model using SEPARATE-Seq. Nature Communications, /, /. https://doi.org/10.1038/s41467-026-72247-5 (Original work published 2026)