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| Item Type: | Article |
|---|---|
| Title: | The single-cell transcriptional landscape of lung carcinoid tumors |
| Creators: |
Bischoff, P.  ORCID: https://orcid.org/0000-0002-4442-7116, Trinks, A. ORCID: https://orcid.org/0000-0001-9983-1506, Wiederspahn, J. ORCID: https://orcid.org/0000-0003-0117-9754, Obermayer, B. ORCID: https://orcid.org/0000-0002-9116-630X, Pett, J.P. ORCID: https://orcid.org/0000-0002-5249-444X, Jurmeister, P. ORCID: https://orcid.org/0000-0001-7745-3794, Elsner, A., Dziodzio, T. ORCID: https://orcid.org/0000-0002-3337-4573, Rückert, J.C., Neudecker, J., Falk, C. ORCID: https://orcid.org/0000-0003-1376-7318, Beule, D. ORCID: https://orcid.org/0000-0002-3284-0632, Sers, C. ORCID: https://orcid.org/0000-0002-6219-1514, Morkel, M. ORCID: https://orcid.org/0000-0002-2553-9999, Horst, D. ORCID: https://orcid.org/0000-0003-4755-5743, Klauschen, F. ORCID: https://orcid.org/0000-0002-9131-2389 and Blüthgen, N. ORCID: https://orcid.org/0000-0002-0171-7447
|
| Abstract: | 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 non-inflammatory 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 non-inflammatory and vessel-rich nature of their tumor microenvironment, and outlining relevant intercellular interactions which could serve as future therapeutic targets. |
| Keywords: | Carcinoid Tumors, Lung Cancer, Neuroendocrine Tumors, Single-Cell Transcriptomics, Tumor Microenvironment |
| Source: | International Journal of Cancer |
| ISSN: | 0020-7136 |
| Publisher: | Wiley |
| Volume: | 150 |
| Number: | 12 |
| Page Range: | 2058-2071 |
| Date: | 15 June 2022 |
| Official Publication: | https://doi.org/10.1002/ijc.33995 |
| PubMed: | View item in PubMed |
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