Single-cell and spatial transcriptomics analysis of non-small cell lung cancer

Marco Zuani, Haoliang Xue, Jun Sung Park, Stefan C. Dentro, Zaira Seferbekova, Julien Tessier, Sandra Curras-Alonso, Angela Hadjipanayis, Emmanouil I. Athanasiadis, Moritz Gerstung, Omer Bayraktar and Ana Cvejic ()
Additional contact information
Marco Zuani: Wellcome Genome Campus
Haoliang Xue: Wellcome Genome Campus
Jun Sung Park: Wellcome Genome Campus
Stefan C. Dentro: Wellcome Genome Campus
Zaira Seferbekova: Wellcome Genome Campus
Julien Tessier: Sanofi
Sandra Curras-Alonso: Sanofi
Angela Hadjipanayis: Sanofi
Emmanouil I. Athanasiadis: Wellcome Genome Campus
Moritz Gerstung: Wellcome Genome Campus
Omer Bayraktar: Wellcome Genome Campus
Ana Cvejic: Wellcome Genome Campus

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Lung cancer is the second most frequently diagnosed cancer and the leading cause of cancer-related mortality worldwide. Tumour ecosystems feature diverse immune cell types. Myeloid cells, in particular, are prevalent and have a well-established role in promoting the disease. In our study, we profile approximately 900,000 cells from 25 treatment-naive patients with adenocarcinoma and squamous-cell carcinoma by single-cell and spatial transcriptomics. We note an inverse relationship between anti-inflammatory macrophages and NK cells/T cells, and with reduced NK cell cytotoxicity within the tumour. While we observe a similar cell type composition in both adenocarcinoma and squamous-cell carcinoma, we detect significant differences in the co-expression of various immune checkpoint inhibitors. Moreover, we reveal evidence of a transcriptional “reprogramming” of macrophages in tumours, shifting them towards cholesterol export and adopting a foetal-like transcriptional signature which promotes iron efflux. Our multi-omic resource offers a high-resolution molecular map of tumour-associated macrophages, enhancing our understanding of their role within the tumour microenvironment.

Date: 2024
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DOI: 10.1038/s41467-024-48700-8

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