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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE157883 | 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 (0Gy4Gy scRNA-seq)

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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 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.

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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 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 (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)

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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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