Spatial downregulation of CD74 signatures may drive invasive component development in part-solid lung adenocarcinoma

Zhang, Jia-Tao; Zhang, Juan; Wang, Song-Rong; Yan, Li-Xu; Qin, Jing; Yin, Kai; Chu, Xiang-Peng; Wang, Meng-Min; Hong, Hui-Zhao; Lv, Zhi-Yi; Dong, Song; Jiang, Ben-Yuan; Zhang, Xu-Chao; Liu, Xiang; Zhou, Qing; Wu, Yi-Long; Zhong, Wen-Zhao

doi:10.1016/j.isci.2023.107699

Cited by 4 publications

(2 citation statements)

References 43 publications

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“…More recently, using scRNA sequencing, M1-like pro-inflammatory macrophages have been implicated in remission from acute myeloid leukemia [5], and as correlates of protection in patients with lung cancers [6].…”

Section: Single Cell Rna (Scrna) Sequencing Has Revealed the Importan...mentioning

confidence: 99%

Antibody Dependent Enhancement (ADE) of Infection into Macrophages Validates the Importance of HERV-K102 Particle Production for Pandemic Preparedness

Laderoute

2023

Preprint

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Historically, macrophages have been long implicated in the control of the severity of infectious diseases. This has been based on the observations of a higher risk of severe disease and death upon rechallenge with viral variants due to antibody dependent enhance-ment (ADE) of infection into macrophages. The question remains as to what can account for this potent heterologous protection in macrophages? Here it is argued that the elusive defense mechanism of M1-like pro-inflammatory macrophages may pertain to a novel virus anti-virus response. This system initiates with high replication of human endogenous retrovirus K102 (HERV-K102), a non-pathogenic, protector foamy retrovirus of humans which generates M1-like pro-inflammatory foamy macrophages, glycolysis, and epigenetic changes, all characteristic of trained immunity. This virus-anti-virus system kills virally infected cells by several mechanisms, amplifies the innate interferon response via ‘viral mimicry’, has many unique components that interfere with exoge-nous virus replication, and may be especially adept at neutralizing enveloped exogenous pandemic viruses, such as SARS-CoV-2 and HIV-1. The goal of this treatise is to introduce the multifaceted HERV-K102 protector system, to illustrate how SARS-CoV-2 may target the HERV-K102 protector system by ADE, and to explore how this innate defense system may be exploited for pandemic preparedness.

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Section: Single Cell Rna (Scrna) Sequencing Has Revealed the Importan...mentioning

confidence: 99%

Antibody Dependent Enhancement (ADE) of Infection into Macrophages Validates the Importance of HERV-K102 Particle Production for Pandemic Preparedness

Laderoute

2023

Preprint

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“…A recent scRNA‐seq study in subsolid pulmonary nodules identified two subpopulations of epithelial cells (EPs), one of which showed upregulation of inflammatory features only, and demonstrated spatial transcriptomic similarity of this cell subpopulation to the lepidic histological subtype. 16 This suggested the possibility of histological typing by scRNA‐seq based on spatial transcriptomics technology, which can capture different cell types and thus obtain the characteristic genes profiles of different histological subtypes.…”

Section: Introductionmentioning

confidence: 99%

Spatial transcriptomics reveals heterogeneity of histological subtypes between lepidic and acinar lung adenocarcinoma

Xie,

Kong,

et al. 2024

Clinical & Translational Med

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BackgroundPatients who possess various histological subtypes of early‐stage lung adenocarcinoma (LUAD) have considerably diverse prognoses. The simultaneous existence of several histological subtypes reduces the clinical accuracy of the diagnosis and prognosis of early‐stage LUAD due to intratumour intricacy.MethodsWe included 11 postoperative LUAD patients pathologically confirmed to be stage IA. Single‐cell RNA sequencing (scRNA‐seq) was carried out on matched tumour and normal tissue. Three formalin‐fixed and paraffin‐embedded cases were randomly selected for 10× Genomics Visium analysis, one of which was analysed by digital spatial profiler (DSP).ResultsUsing DSP and 10× Genomics Visium analysis, signature gene profiles for lepidic and acinar histological subtypes were acquired. The percentage of histological subtypes predicted for the patients from samples of 11 LUAD fresh tissues by scRNA‐seq showed a degree of concordance with the clinicopathologic findings assessed by visual examination. DSP proteomics and 10× Genomics Visium transcriptomics analyses revealed that a negative correlation (Spearman correlation analysis: r = –.886; p = .033) between the expression levels of CD8 and the expression trend of programmed cell death 1(PD‐L1) on tumour endothelial cells. The percentage of CD8+ T cells in the acinar region was lower than in the lepidic region.ConclusionsThese findings illustrate that assessing patient histological subtypes at the single‐cell level is feasible. Additionally, tumour endothelial cells that express PD‐L1 in stage IA LUAD suppress immune‐responsive CD8+ T cells.

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Multi-omics analysis unveils immunosuppressive microenvironment in the occurrence and development of multiple pulmonary lung cancers

Zhang,

Zhou,

et al. 2024

npj Precis. Onc.

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Multiple pulmonary lung cancers (MPLCs) are frequently encountered on computed tomography (CT) scanning of chest, yet their intrinsic characteristics associated with genomic features and radiological or pathological textures that may lead to distinct clinical outcomes remain largely unexplored. A total of 27 pulmonary nodules covering different radiological or pathological textures as well as matched adjacent normal tissues and blood samples were collected from patients diagnosed with MPLCs. Whole-exome sequencing (WES) and whole-transcriptome sequencing were performed. The molecular and immune features of MPLCs associated with distinct radiological or pathological textures were comprehensively investigated. Genomics analysis unveiled the distinct branches of pulmonary nodules originating independently within the same individual. EGFR and KRAS mutations were found to be prevalent in MPLCs, exhibiting mutual exclusivity. The group with KRAS mutations exhibited stronger immune signatures compared to the group with EGFR mutations. Additionally, MPLCs exhibited a pronounced immunosuppressive microenvironment, which was particularly distinct when compared with normal tissues. The expression of the FDSCP gene was specifically observed in MPLCs. When categorizing MPLCs based on radiological or pathological characteristics, a progressive increase in mutation accumulation was observed, accompanied by heightened chromatin-level instability as ground-glass opacity component declined or invasive progression occurred. A close association with the immunosuppressive microenvironment was also observed during the progression of pulmonary nodules. Notably, the upregulation of B cell and regulatory T cell marker genes occurred progressively. Immune cell abundance analysis further demonstrated a marked increase in exhausted cells and regulatory T cells during the progression of pulmonary nodules. These results were further validated by independent datasets including nCounter RNA profiling, single-cell RNA sequencing, and spatial transcriptomic datasets. Our study provided a comprehensive representation of the diverse landscape of MPLCs originating within the same individual and emphasized the significant influence of the immunosuppressive microenvironment in the occurrence and development of pulmonary nodules. These findings hold great potential for enhancing the clinical diagnosis and treatment strategies for MPLCs.

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Spatial downregulation of CD74 signatures may drive invasive component development in part-solid lung adenocarcinoma

Cited by 4 publications

References 43 publications

Antibody Dependent Enhancement (ADE) of Infection into Macrophages Validates the Importance of HERV-K102 Particle Production for Pandemic Preparedness

Antibody Dependent Enhancement (ADE) of Infection into Macrophages Validates the Importance of HERV-K102 Particle Production for Pandemic Preparedness

Spatial transcriptomics reveals heterogeneity of histological subtypes between lepidic and acinar lung adenocarcinoma

Multi-omics analysis unveils immunosuppressive microenvironment in the occurrence and development of multiple pulmonary lung cancers

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