Non-small cell lung cancer (NSCLC) contains a diversity of histological subtypes and specific mutational signatures. Single-cell RNA sequencing (scRNA-seq) technologies have enabled the characterisation of the NSCLC tumour microenvironment (TME).

However, there is a lack of understanding on how different immune cell phenotypes may contribute to therapy resistance. There is a paucity of data on neutrophils, which may mediate pro- and anti-tumour inflammatory pathways.

Atlas maps cells from patients with non-small cell lung cancer¹

Salcher et al. built a comprehensive, large-scale NSCLC scRNA-seq atlas out of 29 datasets from 19 studies with 556 samples containing 1,283,972 cells. This atlas includes a total of 318 individuals (232 patients with NSCLC and 86 non-cancer controls).

Using the atlas, they stratified patients with NSCLC based on the infiltration patterns of their TMEs. By analysing the genomic and clinical information of bulk samples, they stratified the patients into four separate tumour immune phenotypes.

Tumour immune phenotypes¹

1. Immune-deserted tumours
2. B-cell tumours
3. Myeloid tumours
4. T-cell tumours

For each of the four immune phenotypes, they then identified tumour-cell-based TME imprinting characteristics.

Focus on neutrophils¹

To make up for the lack of neutrophil single-cell data, they included samples from 17 patients with NSCLC. They carried out an in-depth characterisation of tissue-resident neutrophils (TRNs), including tumor-associated neutrophils (TANs) and normal adjacent tissue-associated neutrophils (NANs), using the BD Rhapsody™ Single-Cell Analysis System.

One of the TAN subsets appears to present antigen-like properties at the tumour site. This may generate anti-tumour immunity. They also found evidence linking TRNs to therapy failure using a gene signature specific to TANs.

This large-scale atlas provides us with a better understanding of the characteristics of TRN subsets in NSCLC.

Read the full study: High-resolution single-cell atlas reveals diversity and plasticity of tissue-resident neutrophils in non-small cell lung cancer

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