ArticleJournal of translational medicine2022
Comparative profiling of single-cell transcriptome reveals heterogeneity of tumor microenvironment between solid and acinar lung adenocarcinoma.
Article in Journal of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Proteogenomic characterization of pulmonary large-cell neuroendocrine carcinoma identifies molecular features and therapeutic strategy.Science advances · 2026Article
- Defining the cellular and molecular identities of histologic subtypes in lung adenocarcinoma.Experimental hematology & oncology · 2026Article
- Effect of spatial resolution on the diagnostic performance of machine-learning radiomics model in lung adenocarcinoma: comparisons between normal- and high-spatial-resolution imaging for predicting invasiveness.Japanese journal of radiology · 2025Article
- Theranostic Potential of Copper-64 ATSM Targeting MTHFD2: An In Silico Perspective on Hypoxia-Selective Imaging and Therapy.Cell biochemistry and biophysics · 2025Article
- Article
- Impact of histopathological subtypes on invasive lung adenocarcinoma: from epidemiology to tumour microenvironment to therapeutic strategies.World journal of surgical oncology · 2025Review
- Promotion Mechanisms of Stromal Cell-Mediated Lung Cancer Development Within Tumor Microenvironment.Cancer management and research · 2025Review
- Acquisition of discrete immune suppressive barriers contributes to the initiation and progression of preinvasive to invasive human lung cancer.bioRxiv : the preprint server for biology · 2025Article
- IRF8 deficiency-induced myeloid-derived suppressor cell promote immune evasion in lung adenocarcinoma.Journal of translational medicine · 2024Article
- Unlocking the potential of T-cell metabolism reprogramming: Advancing single-cell approaches for precision immunotherapy in tumour immunity.Clinical and translational medicine · 2024Review
- Impact of lung adenocarcinoma subtypes on survival and timing of brain metastases.Frontiers in oncology · 2024Article
- Computed tomography imaging and clinical characteristics of pulmonary ground-glass nodules ≤2 cm with micropapillary pattern.Thoracic cancer · 2023Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
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Abstract
backgroundThe diversity of histologic composition reflects the inter- and intra-tumor heterogeneity of lung adenocarcinomas (LUADs) macroscopically. Insights into the oncological characteristics and tumor microenvironment (TME) of different histologic subtypes of LUAD at the single-cell level can help identify potential therapeutic vulnerabilities and combinational approaches to improve the survival of LUAD patients.
methodsThrough comparative profiling of cell communities defined by scRNA-seq data, we characterized the TME of LUAD samples of distinct histologic subtypes, with relevant results further confirmed in multiple bulk transcriptomic, proteomic datasets and an independent immunohistochemical validation cohort.
resultsWe find that the hypoxic and acidic situation is the worst in the TME of solid LUADs compared to other histologic subtypes. Besides, the tumor metabolic preferences vary across histologic subtypes and may correspondingly impinge on the metabolism and function of immune cells. Remarkably, tumor cells from solid LUADs upregulate energy and substance metabolic activities, particularly the folate-mediated one-carbon metabolism and the key gene MTHFD2, which could serve as a potential therapeutic target. Additionally, ubiquitination modifications may also be involved in the progression of histologic patterns. Immunologically, solid LUADs are characterized by a predominance of exhausted T cells and immunosuppressive myeloid cells, where the hypoxic, acidified and nutrient-deprived TME has a non-negligible impact. Discrepancies in stromal cell function, evidenced by varying degrees of stromal remodeling and fibrosis, may also contribute to the specific immune phenotype of solid LUADs.
conclusionsOverall, our research proposes several potential entry points to improve the immunosuppressive TME of solid LUADs, thereby synergistically potentiating their immunotherapeutic efficacy, and may provide precise therapeutic strategies for LUAD patients of distinct histologic subtype constitution.
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