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Radiation-activated secretome of Scgb1a1+ club cells increase the efficacy of immune checkpoint blockade in lung cancer (0Gy4Gy scRNA-seq)

ABSTRACT: We report that airway epithelial club cells harbor the genes specifically up-regulated by 4Gy-RT

ORGANISM(S): Mus musculus

PROVIDER: GSE157881 | GEO | 2021/06/08

REPOSITORIES: GEO

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Radiation-activated secretome of Scgb1a1+ club cells increase the efficacy of immune checkpoint blockade in lung cancer (iDTR scRNA-seq)

Project description:We report that airway epithelial club cells affected the immune landscaping in HKP1 lungs

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Radiation-activated secretome of Scgb1a1+ club cells increase the efficacy of immune checkpoint blockade in lung cancer (Bulk048 RNA-seq)

Project description:We uncovered an essential role of radiationtherapy (RT)-activated lung residential Scgb1a1+ club cells in synergizing efficacy of immuno-checkpoint inhibitors. We explored the mechanisms underlying RT by analyzing the differentially-regulated genes in tumor micro-environment.

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Radiation-activated secretome of Scgb1a1+ club cells increase the efficacy of immune checkpoint blockade in lung cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-06-08 | GSE157883 | GEO

Radiation-activated secretome of Scgb1a1+ club cells increase the efficacy of immune checkpoint blockade in lung cancer

Project description:Radiation-activated secretome of Scgb1a1+ club cells increase the efficacy of immune checkpoint blockade in lung cancer

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Radiation-activated secretory proteins of <i>Scgb1a1</i><sup>+</sup> club cells increase the efficacy of immune checkpoint blockade in lung cancer.

Project description:Radiation therapy (RT) in combination with immune checkpoint inhibitor (ICI) represents a promising regimen for non-small cell lung cancer (NSCLC), however, the underlying mechanisms are poorly characterized. We identified a specific dose of RT that conferred tumor regression and improved survival in NSCLC models when combined with ICI. The immune-modulating functions of RT was ascribed to activated lung-resident Scgb1a1+ club cells. Importantly, mice with club cell-specific knockout of synaptosome-associated protein 23 failed to benefit from the combination treatment, indicating a pivotal role of club cell secretome. We identified 8 club cells secretory proteins, which inhibited immunosuppressive myeloid cells, reduced pro-tumor inflammation, and enhanced anti-tumor immunity. Notably, CC10, a member of club cell secretome was increased in plasma of NSCLC patients responding to the combination therapy. By revealing an immune-regulatory role of club cells, our studies have the potential to guide future clinical trials of ICI in NSCLC.

| S-EPMC8670735 | biostudies-literature

Radiation-activated secretome of Scgb1a1+ club cells increase the efficacy of immune checkpoint blockade in lung cancer (Bulk048 RNA-seq)

Project description:Radiation-activated secretome of Scgb1a1+ club cells increase the efficacy of immune checkpoint blockade in lung cancer (Bulk048 RNA-seq)

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Radiation-activated secretome of Scgb1a1+ club cells increase the efficacy of immune checkpoint blockade in lung cancer (iDTR scRNA-seq)

Project description:Radiation-activated secretome of Scgb1a1+ club cells increase the efficacy of immune checkpoint blockade in lung cancer (iDTR scRNA-seq)

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Radiation-activated secretome of Scgb1a1+ club cells increase the efficacy of immune checkpoint blockade in lung cancer (0Gy4Gy scRNA-seq)

Project description:Radiation-activated secretome of Scgb1a1+ club cells increase the efficacy of immune checkpoint blockade in lung cancer (0Gy4Gy scRNA-seq)

| PRJNA663166 | ENA

Bronchiolar progenitors and club cells in mouse lung

Project description:Gene expression patterns of bronchiolar progenitors and club cells in mouse lung were examined by microarray experiments. Although it has not yet been fully characterized, a subset of epithelial cells lining bronchioles are best understood as bronchiolar progenitors that self-renew over the long term and that can differentiate into more differentiated club cells and ciliated cells. The bronchiolar progenitors are distinct from club cells and characteristically express the alveolar type 2 cell marker, prosurfactant protein C, with lower levels of club cell secretory protein/Scgb1a1. There are also functional differences between them; while club cells can be depleted by naphthalene because of the abundance of cytochrome P450 enzyme Cyp2f2, bronchiolar progenitors are resistant to naphthalene-induced depletion because of defects in the enzyme.

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Targeting Multiple Receptors to Increase Checkpoint Blockade Efficacy.

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