Single-cell profiling of tumor heterogeneity and the microenvironment in advanced non-small cell lung cancer

TLDR

Lung cancer is a highly heterogeneous disease in which cancer cells and the tumor microenvironment jointly determine disease progression, treatment response, and immune escape. The study aims to map the cell type‑specific transcriptome landscape of cancer cells and their tumor microenvironment in advanced NSCLC by analyzing 42 stage III/IV biopsy samples with single‑cell RNA sequencing. The authors performed single‑cell RNA sequencing on 42 stage III/IV NSCLC biopsy samples to generate large‑scale, single‑cell resolution profiles. The analysis revealed rare cell types such as follicular dendritic cells and T helper 17 cells, extensive inter‑patient heterogeneity in cellular composition, chromosomal structure, developmental trajectories, signaling networks, and phenotype dominance, and a correlation between tumor heterogeneity and tumor‑associated neutrophils.

Abstract

Abstract Lung cancer is a highly heterogeneous disease. Cancer cells and cells within the tumor microenvironment together determine disease progression, as well as response to or escape from treatment. To map the cell type-specific transcriptome landscape of cancer cells and their tumor microenvironment in advanced non-small cell lung cancer (NSCLC), we analyze 42 tissue biopsy samples from stage III/IV NSCLC patients by single cell RNA sequencing and present the large scale, single cell resolution profiles of advanced NSCLCs. In addition to cell types described in previous single cell studies of early stage lung cancer, we are able to identify rare cell types in tumors such as follicular dendritic cells and T helper 17 cells. Tumors from different patients display large heterogeneity in cellular composition, chromosomal structure, developmental trajectory, intercellular signaling network and phenotype dominance. Our study also reveals a correlation of tumor heterogeneity with tumor associated neutrophils, which might help to shed light on their function in NSCLC.