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Intertumoral lineage diversity and immunosuppressive transcriptional programs in well-differentiated gastroenteropancreatic neuroendocrine tumors. | LitMetric

AI Article Synopsis

  • * A study analyzed the single-cell gene expression of tumor and immune cells from patients with gastroenteropancreatic NETs, revealing that cancer cells retained certain characteristics of normal endocrine cells and showed varied immune checkpoint expressions.
  • * The research underscores the complexity of GEP-NETs and suggests new possibilities for personalized treatment strategies based on the distinct cellular environments and gene expression patterns of different tumor subtypes.

Article Abstract

Neuroendocrine tumors (NETs) are rare cancers that most often arise in the gastrointestinal tract and pancreas. The fundamental mechanisms driving gastroenteropancreatic (GEP)-NET growth remain incompletely elucidated; however, the heterogeneous clinical behavior of GEP-NETs suggests that both cellular lineage dynamics and tumor microenvironment influence tumor pathophysiology. Here, we investigated the single-cell transcriptomes of tumor and immune cells from patients with gastroenteropancreatic NETs. Malignant GEP-NET cells expressed genes and regulons associated with normal, gastrointestinal endocrine cell differentiation, and fate determination stages. Tumor and lymphoid compartments sparsely expressed immunosuppressive targets commonly investigated in clinical trials, such as the programmed cell death protein-1/programmed death ligand-1 axis. However, infiltrating myeloid cell types within both primary and metastatic GEP-NETs were enriched for genes encoding other immune checkpoints, including (VISTA), (TIM3), (Gal-9), and . Our findings highlight the transcriptomic heterogeneity that distinguishes the cellular landscapes of GEP-NET anatomic subtypes and reveal potential avenues for future precision medicine therapeutics.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10530100PMC
http://dx.doi.org/10.1126/sciadv.add9668DOI Listing

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