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<p>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.</p>

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Multiomics immune profiling of a patient-relevant orthotopic lung cancer model using SEPARATE-Seq

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月23日

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  • Pauline M. R. Bardet,
  • Lize Allonsius,
  • Eva Hadadi,
  • Daliya Kancheva,
  • Morgane Paque,
  • Sarka Vosahlikova,
  • Aarushi A. Caro,
  • Anouk Van Audenhove,
  • Ayla Debraekeleer,
  • Ria Roelandt,
  • Kevin Verstaen,
  • Michal Hensler,
  • Delphine Hoton,
  • Gisèle Mateu Cabrera,
  • Louis Boon,
  • Arnaud Blomme,
  • Sofie Deschoemaeker,
  • Geert Raes,
  • Elly Marcq,
  • Ahmed E. I. Hamouda,
  • Jan P. Böttcher,
  • Jitka Fucikova,
  • Pierre Close,
  • Frank Aboubakar Nana,
  • Damya Laoui

摘要

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.