The heterogeneous immune landscape between lung adenocarcinoma and squamous carcinoma revealed by single-cell RNA sequencing

A thorough interrogation of the immune landscape is crucial for immunotherapy strategy selection and prediction of clinical responses in non-small-cell lung cancer (NSCLC) patients. Single-cell RNA sequencing (scRNA-seq) techniques have prompted the opportunity to dissect the distinct immune signatures between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), the two major subtypes of NSCLC. Here, we performed scRNA-seq on 72,475 immune cells from 40 samples of tumor and matched adjacent normal tissues spanning 19 NSCLC patients, and drew a systematic immune cell transcriptome atlas. Joint analyses of the distinct cellular compositions, differentially expressed genes (DEGs), cell-cell interactions, pseudotime trajectory, transcriptomic factors and prognostic factors based on The Cancer Genome Atlas (TCGA), revealed the central roles of cytotoxic and effector T and NK cells and the distinct functional macrophages (M phi) subtypes in the immune microenvironment heterogeneity between LUAD and LUSC. The dominant subtype of M phi was FABP4-M phi in LUAD and SPP1-M phi in LUSC. Importantly, we identified a novel lymphocyte-related M phi cluster, which we named SELENOP-M phi, and further established its antitumor role in both types, especially in LUAD. Our comprehensive depiction of the immune heterogeneity and definition of M phi clusters could help design personalized treatment for lung cancer patients in clinical practice.