| First Author | Ban Y | Year | 2021 |
| Journal | Nat Cancer | Volume | 2 |
| Issue | 9 | Pages | 919-931 |
| PubMed ID | 34917944 | Mgi Jnum | J:321549 |
| Mgi Id | MGI:6885690 | Doi | 10.1038/s43018-021-00245-1 |
| Citation | Ban Y, et al. (2021) Radiation-activated secretory proteins of Scgb1a1 (+) club cells increase the efficacy of immune checkpoint blockade in lung cancer. Nat Cancer 2(9):919-931 |
| abstractText | 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. |
