| First Author | Yuan B | Year | 2022 |
| Journal | JCI Insight | Volume | 7 |
| Issue | 11 | PubMed ID | 35471938 |
| Mgi Jnum | J:326200 | Mgi Id | MGI:7294945 |
| Doi | 10.1172/jci.insight.157788 | Citation | Yuan B, et al. (2022) Targeting IL-1beta as an immunopreventive and therapeutic modality for K-ras-mutant lung cancer. JCI Insight 7(11):e157788 |
| abstractText | K-ras-mutant lung adenocarcinoma (KM-LUAD) is associated with abysmal prognosis and is tightly linked to tumor-promoting inflammation. A human mAb, canakinumab, targeting the proinflammatory cytokine IL-1beta, significantly decreased the risk of lung cancer in the Canakinumab Anti-inflammatory Thrombosis Outcomes Study. Interestingly, we found high levels of IL-1beta in the lungs of mice with K-rasG12D-mutant tumors (CC-LR mice). Here, we blocked IL-1beta using an anti-IL-1beta mAb in cohorts of 6- or 14-week-old CC-LR mice to explore its preventive and therapeutic effect, respectively. IL-1beta blockade significantly reduced lung tumor burden, which was associated with reprogramming of the lung microenvironment toward an antitumor phenotype characterized by increased infiltration of cytotoxic CD8+ T cells (with high IFN-gamma and granzyme B expression but low programmed cell death 1 [PD-1] expression) while suppressing neutrophils and polymorphonuclear (PMN) myeloid-derived suppressor cells. When querying the Cancer Genome Atlas data set, we found positive correlations between IL1B expression and infiltration of immunosuppressive PMNs and expression of their chemoattractant, CXCL1, and PDCD1 expressions in patients with KM-LUAD. Our data provide evidence that IL-1beta blockade may be a preventive strategy for high-risk individuals and an alternative therapeutic approach in combination with currently available treatments for KM-LUAD. |
