Single-cell sequencing reveals immune landscape of tumor-infiltrating lymphocytes (TILs) during non-small cell lung cancer (NSCLC) progression

Abstract During the process of NSCLC using TILs therapy, the heterogeneity of immune cell was revealed by using combined single-cell RNA (scRNA)/ T cell receptor (scTCR) sequencing -seq data from lung adenocarcinoma (LUAD) patients. Naïve CD4+ T was increased in tumor tissue compared with circulating blood samples, activated signaling pathways were recognized, and GZMA was identified as a potential novel diagnostic biomarker. The scTCR-seq repertoire was also investigated. At transition state, macrophages (FTL) and dendritic (AIF1) cells transferred the most CD3 TCR clones to T (IL7R) cells, and cytotoxicity (NKG7) transported to terminal exhausted (CCL5) CD8+ T cells. At transition and expansion state, T helper (CXCL13) transported the most CD3 TCR clones to regulatory T (FOXP3) cells. The expression profiling of cytokines, checkpoint receptors and their ligands during tumor progression were also investigated. T helper (FTL, TNFRSF4 and TIGIT) and regulatory T (CTLA4, TIGIT and FTL) show up at the initial stage of normal and metastatic samples, while cytotoxicity (FGFBP2, NKG7, PRF1 and CCL5) CD8+ T cells still appears at the final stage of normal and metastatic samples. Taken together, our study provides the single cell level of TILs in NSCLC and offers treatment strategies to overcome drug resistance.