Data from Single-cell characterization of pulmonary nodules implicates suppression of immunosurveillance across early stages of lung adenocarcinoma Article Swipe

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Jane Yanagawa , Linh M. Tran , Ramin Salehi‐Rad , Raymond J. Lim , Camelia Dumitras , Eileen Fung , W. Dean Wallace , Ashley E. Prosper , Gregory A. Fishbein , Conor Shea , Rui Hong , Bitta Kahangi , John Deng , Adam C. Gower , Bin Liu , Joshua D. Campbell , Sarah A. Mazzilli , Jennifer Beane , Humam Kadara , Marc E. Lenburg , Avrum Spira , Denise R. Aberle , Kostyantyn Krysan , Steven M. Dubinett ·

YOU? · · 2024 · Open Access · · DOI: https://doi.org/10.1158/0008-5472.c.6861221.v2

A greater understanding of molecular, cellular, and immunological changes during the early stages of lung adenocarcinoma development could improve diagnostic and therapeutic approaches in patients with pulmonary nodules at risk for lung cancer. To elucidate the immunopathogenesis of early lung tumorigenesis, we evaluated surgically resected pulmonary nodules representing the spectrum of early lung adenocarcinoma as well as associated normal lung tissues utilizing single-cell RNA sequencing and validated the results by flow cytometry and multiplex immunofluorescence. Single-cell transcriptomics revealed a significant decrease in gene expression associated with cytolytic activities of tumor-infiltrating natural killer and natural killer T cells. This was accompanied by a reduction in effector T cells and an increase of CD4+ regulatory T cells in subsolid nodules. An independent set of resected pulmonary nodules consisting of both adenocarcinomas and associated premalignant lesions corroborated the early increment of regulatory T cells in premalignant lesions compared to the associated normal lung tissues by multiplex immunofluorescence. Gene expression analysis indicated that cancer-associated alveolar type 2 cells and fibroblasts may contribute to the deregulation of the extracellular matrix, potentially affecting immune infiltration in subsolid nodules through ligand-receptor interactions. These findings suggest that there is a suppression of immune surveillance across the spectrum of early-stage lung adenocarcinoma.

Related Topics

Adenocarcinoma Of The Lung

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Immunosurveillance Lung Adenocarcinoma Pathology Pulmonary adenocarcinoma Cell Biology Medicine Chemistry Internal medicine Cancer Biochemistry

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Type: preprint
Language: en
Landing Page: http://doi.org/10.1158/0008-5472.c.6861221.v2
OA Status: gold
Related Works: 10
OpenAlex ID: https://openalex.org/W4402803294

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DOI: https://doi.org/10.1158/0008-5472.c.6861221.v2

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Title: Data from Single-cell characterization of pulmonary nodules implicates suppression of immunosurveillance across early stages of lung adenocarcinoma

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Type: preprint

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Language: en

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Publication year: 2024

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Publication date: 2024-09-16

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Authors: Jane Yanagawa, Linh M. Tran, Ramin Salehi‐Rad, Raymond J. Lim, Camelia Dumitras, Eileen Fung, W. Dean Wallace, Ashley E. Prosper, Gregory A. Fishbein, Conor Shea, Rui Hong, Bitta Kahangi, John Deng, Adam C. Gower, Bin Liu, Joshua D. Campbell, Sarah A. Mazzilli, Jennifer Beane, Humam Kadara, Marc E. Lenburg, Avrum Spira, Denise R. Aberle, Kostyantyn Krysan, Steven M. Dubinett

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Landing page: https://doi.org/10.1158/0008-5472.c.6861221.v2

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OA status: gold

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OA URL: https://doi.org/10.1158/0008-5472.c.6861221.v2

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Concepts: Immunosurveillance, Lung, Adenocarcinoma, Pathology, Pulmonary adenocarcinoma, Cell, Biology, Medicine, Chemistry, Internal medicine, Cancer, Biochemistry

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abstract_inverted_index.accompanied	99
abstract_inverted_index.development	16
abstract_inverted_index.early-stage	200
abstract_inverted_index.fibroblasts	165
abstract_inverted_index.independent	119
abstract_inverted_index.potentially	175
abstract_inverted_index.significant	79
abstract_inverted_index.single-cell	62
abstract_inverted_index.suppression	192
abstract_inverted_index.therapeutic	21
abstract_inverted_index.corroborated	133
abstract_inverted_index.deregulation	170
abstract_inverted_index.infiltration	178
abstract_inverted_index.premalignant	131, 142
abstract_inverted_index.representing	47
abstract_inverted_index.surveillance	195
abstract_inverted_index.extracellular	173
abstract_inverted_index.immunological	7
abstract_inverted_index.interactions.	184
abstract_inverted_index.understanding	2
abstract_inverted_index.adenocarcinoma	15, 53
abstract_inverted_index.tumorigenesis,	40
abstract_inverted_index.adenocarcinomas	128
abstract_inverted_index.ligand-receptor	183
abstract_inverted_index.transcriptomics	76
abstract_inverted_index.cancer-associated	159
abstract_inverted_index.immunopathogenesis	36
abstract_inverted_index.tumor-infiltrating	89
abstract_inverted_index.immunofluorescence.	74, 153
abstract_inverted_index.<div>Abstract<p>A	0
abstract_inverted_index.adenocarcinoma.</p></div>	202
cited_by_percentile_year
countries_distinct_count	0
institutions_distinct_count	24
citation_normalized_percentile.value	0.33032751
citation_normalized_percentile.is_in_top_1_percent	False
citation_normalized_percentile.is_in_top_10_percent	False