Targeting IL-1β as an immunopreventive and therapeutic modality for K-ras-mutant lung cancer.

ABSTRACT: 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-1β, significantly decreased the risk of lung cancer in the Canakinumab Anti-inflammatory Thrombosis Outcomes Study. Interestingly, we found high levels of IL-1β in the lungs of mice with K-rasG12D-mutant tumors (CC-LR mice). Here, we blocked IL-1β using an anti-IL-1β mAb in cohorts of 6- or 14-week-old CC-LR mice to explore its preventive and therapeutic effect, respectively. IL-1β 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 cel

SUBMITTER: Yuan B 

PROVIDER: S-EPMC9220853 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature