Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features.
Hitoshi DejimaXin HuRunzhe ChenJianhua ZhangJunya FujimotoEdwin Roger Parra CuentesCara L HaymakerShawna Marie HubertDzifa DuoseLuisa Maren Solis SotoDan SuJunya FukuokaKazuhiro TabataHoa H N PhamNicholas McgranahanBaili ZhangJie YeLisha YingLatasha LittleCurtis GumbsChi-Wan ChowMarcos Roberto EstecioMyrna C B GodoyMara B AntonoffBoris SepesiHarvey I PassCarmen BehrensJianhua ZhangAra A VaporciyanJohn Victor HeymachPaul ScheetJiun-Kae Jack LeeJia WuP Andrew FutrealAlexandre ReubenHumam KadaraIgnacio I WistubaJianjun ZhangPublished in: Nature communications (2021)
The mechanism by which anti-cancer immunity shapes early carcinogenesis of lung adenocarcinoma (ADC) is unknown. In this study, we characterize the immune contexture of invasive lung ADC and its precursors by transcriptomic immune profiling, T cell receptor (TCR) sequencing and multiplex immunofluorescence (mIF). Our results demonstrate that anti-tumor immunity evolved as a continuum from lung preneoplasia, to preinvasive ADC, minimally-invasive ADC and frankly invasive lung ADC with a gradually less effective and more intensively regulated immune response including down-regulation of immune-activation pathways, up-regulation of immunosuppressive pathways, lower infiltration of cytotoxic T cells (CTLs) and anti-tumor helper T cells (Th), higher infiltration of regulatory T cells (Tregs), decreased T cell clonality, and lower frequencies of top T cell clones in later-stages. Driver mutations, chromosomal copy number aberrations (CNAs) and aberrant DNA methylation may collectively impinge host immune responses and facilitate immune evasion, promoting the outgrowth of fit subclones in preneoplasia into dominant clones in invasive ADC.
Keyphrases
- regulatory t cells
- copy number
- immune response
- diffusion weighted imaging
- diffusion weighted
- dna methylation
- dendritic cells
- mitochondrial dna
- minimally invasive
- genome wide
- single cell
- gene expression
- magnetic resonance imaging
- contrast enhanced
- transcription factor
- toll like receptor
- rna seq
- robot assisted
- binding protein