Lung carcinoid tumors, also referred to as pulmonary neuroendocrine tumors or lung carcinoids, are rare neoplasms of the lung with a more favorable prognosis than other subtypes of lung cancer. Still, some patients suffer from relapsed disease and metastatic spread. Several recent single-cell studies have provided detailed insights into the cellular heterogeneity of more common lung cancers, such as adeno- and squamous cell carcinoma. However, the characteristics of lung carcinoids on the single-cell level are yet completely unknown. To study the cellular composition and single-cell gene expression profiles in lung carcinoids, we applied single-cell RNA sequencing to three lung carcinoid tumor samples and normal lung tissue. The single-cell transcriptomes of carcinoid tumor cells reflected intertumoral heterogeneity associated with clinicopathological features, such as tumor necrosis and proliferation index. The immune microenvironment was specifically enriched in noninflammatory monocyte-derived myeloid cells. Tumor-associated endothelial cells were characterized by distinct gene expression profiles. A spectrum of vascular smooth muscle cells and pericytes predominated the stromal microenvironment. We found a small proportion of myofibroblasts exhibiting features reminiscent of cancer-associated fibroblasts. Stromal and immune cells exhibited potential paracrine interactions which may shape the microenvironment via NOTCH, VEGF, TGFβ and JAK/STAT signaling. Moreover, single-cell gene signatures of pericytes and myofibroblasts demonstrated prognostic value in bulk gene expression data. Here, we provide first comprehensive insights into the cellular composition and single-cell gene expression profiles in lung carcinoids, demonstrating the noninflammatory and vessel-rich nature of their tumor microenvironment, and outlining relevant intercellular interactions which could serve as future therapeutic targets.

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.33995DOI Listing

Publication Analysis

Top Keywords

lung carcinoids
16
gene expression
16
lung carcinoid
12
single-cell gene
12
expression profiles
12
lung
11
single-cell
8
carcinoid tumors
8
tumors lung
8
insights cellular
8

Similar Publications

Background: Pulmonary carcinoids are rare neuroendocrine tumors accounting for less than 1% of all lung cancers. They are classified into two subcategories; typical and atypical carcinoids with the latter tending to grow faster. Historically, open thoracotomy was the standard approach for pulmonary resection.

View Article and Find Full Text PDF

Small intestinal neuroendocrine tumors (SI-NETs) are characterized by carcinoid syndrome and carcinoid heart disease (CHD). The aim of the present study was to identify early risk markers for carcinoid heart disease and survival in a prospective median-term follow-up setting. We measured 5-HIAA and cumulative 5-HIAA exposure (Cum-5-HIAA) based on repeated measurements, proBNP, vascular function, hepatic tumor load, and transthoracic echocardiography (TTE) at baseline and during the median 5-year follow-up.

View Article and Find Full Text PDF

Neuroendocrine tumor (NET) is a deadly malignancy disease that can be found anywhere in the body. The lack of tumor-specific treatment led to the worse prognosis of NET. Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs), such as alectinib and crizotinib, have been used in the treatment of NET patients with ALK rearrangement.

View Article and Find Full Text PDF

Ectopic adrenocorticotropic hormone (ACTH)-dependent Cushing is a rare syndrome. We present a case that illustrates the diagnostic and therapeutic challenges of ectopic Cushing. A 35-year-old woman presented to the outpatient clinic for evaluation of progressive weight gain, muscle weakness, easy bruising, uncontrolled hypertension, and hyperglycemia.

View Article and Find Full Text PDF
Article Synopsis
  • * The effectiveness of tarlatamab in other cancer types, like DLL3-expressing metastatic pulmonary carcinoid tumors, was previously unknown and lacked approved treatment options.
  • * A patient with a metastatic atypical carcinoid tumor responded positively to tarlatamab after failing several other treatments, suggesting potential benefits for other pulmonary neuroendocrine cancers.
View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!