Single-cell RNA sequencing reveals cellular and molecular immune profile in a Pembrolizumab-responsive PD-L1-negative lung cancer patient.
Runbo ZhongYunbin ZhangDongfang ChenShuhui CaoBaohui HanHua ZhongPublished in: Cancer immunology, immunotherapy : CII (2021)
High expression of PD-L1 predicts PD-1/PD-L1 inhibitor benefit, meanwhile a few PD-L1-negative patients still benefit from these drugs. In this study, we aimed to explore the underlying cellular and molecular characteristics via single-cell sequencing. Before and after treatment with Pembrolizumab, peripheral blood mononuclear cells (PBMCs) were isolated via Ficoll gradient. Thereafter, single-cell RNA sequencing was performed, and clinical significance was validated with The Cancer Genome Atlas (TCGA) cohort. All 3423 cells of 16 clusters were classified into eight cell types, including NKG7+ T, NKG7+ NK, Naïve T, CDC1C+ dendritic cells, CD8+ T cells, B cells, macrophages and erythrocytes. Cell proportion, the clinical significance of differentially expressed genes and significant pathways of NKG7+ T, NKG7+ NK, Naïve T and CD8+ T cells were analyzed. Ubiquitin-mediated proteolysis/cell cycle/natural killer cell-mediated cytotoxicity were identified as PD-1 blockage-responsive pathways in NKG7+ NK cells. Apoptosis/Th1 and Th2 cell differentiation were proposed as Pembrolizumab-affected pathways in NKT cells. In gene level, ID2, PIK3CD, UQCR10, MATK, MZB1, IL7R and TRGC2 showed a significant correlation with PD-1 expression after TCGA dataset validation, which could possess potential as predictive markers for patients with PD-L1-negative lung squamous cell carcinoma who can benefit from Pembrolizumab.
Keyphrases
- single cell
- nk cells
- rna seq
- cell cycle
- high throughput
- cell cycle arrest
- squamous cell carcinoma
- induced apoptosis
- advanced non small cell lung cancer
- dendritic cells
- end stage renal disease
- poor prognosis
- oxidative stress
- gene expression
- chronic kidney disease
- immune response
- cell proliferation
- small molecule
- drug delivery
- regulatory t cells
- signaling pathway
- cancer therapy
- dna methylation
- single molecule
- peritoneal dialysis
- papillary thyroid
- copy number
- human health
- patient reported outcomes