Single-cell and Spatial Transcriptomics Analysis of Non-small Cell Lung Cancer

Overview

Journal Nat Commun

Specialty Biology

Date 2024 May 23

PMID 38782901

Authors

Marco De 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

Ana Cvejic

Affiliations

Soon will be listed here.

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.

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