Single-Cell Transcriptomics of Human and Mouse Lung Cancers Reveals Conserved Myeloid Populations across Individuals and Species

Abstract

Tumor-infiltrating myeloid cells (TIMs) comprise monocytes, macrophages, dendritic cells and neutrophils, and have emerged as key regulators of cancer growth. These cells can diversify into a spectrum of states, which may promote or limit tumor outgrowth, but remain poorly understood. Here, we used single-cell RNA sequencing to map TIMs in non-small cell lung cancer patients. We uncovered 25 TIM states, most of which were reproducibly found across patients. To facilitate translational research of these populations, we also profiled TIMs in mice. In comparing TIMs across species, we identified a near-complete congruence of population structures among dendritic cells and monocytes; conserved neutrophil subsets; and species differences among macrophages. By contrast, myeloid cell population structures in patients’ blood showed limited overlap with those of TIMs. This study determines the lung TIM landscape and sets the stage for future investigations into the potential of TIMs as immunotherapy targets. Tumor-infiltrating myeloid cells (TIM) have emerged as key cancer regulators and potential next-generation immunotherapy targets, yet they remain incompletely understood. Using single cell RNA-seq, Zilionis et al. map the TIM landscape in human and murine lung tumors and systematically compare cell states, revealing conserved myeloid populations across individuals and species.