STK11/LKB1 Deficiency Promotes Neutrophil Recruitment and Proinflammatory Cytokine Production to Suppress T-cell Activity in the Lung Tumor Microenvironment

STK11/LKB1 is among the most commonly inactivated tumor suppressors in non-small cell lung cancer (NSCLC), especially in tumors harboring KRAS mutations. Many oncogenes promote immune escape, undermining the effectiveness of immunotherapies, but it is unclear whether the inactivation of tumor suppressor genes, such as STK11/LKB1, exerts similar effects. In this study, we investigated the consequences of STK11/LKB1 loss on the immune microenvironment in a mouse model of KRAS-driven NSCLC. Genetic ablation of STK11/LKB1 resulted in accumulation of neutrophils with T-cell-suppressive effects, along with a corresponding increase in the expression of T-cell exhaustion markers and tumor-promoting cytokines. The…

• DR
  Damon Runyon Cancer Research Foundation
• UA
  Uniting Against Lung Cancer
• DC
  Dana-Farber Cancer Institute

  Award: Grant Number: SU2CAACR-DT17-15
• DF
  Deutsche Forschungsgemeinschaft

  Award: HE 6897/1-1
• NI
  National Institutes of Health

  Awards: 5R01CA163896-04, 5R01CA122794-10, 5R01CA166480-04, P01 CA120964, R01AI08995, 5R01CA140594-07, 1R01CA195740-01
• NC
  National Cancer Institute

  Award: P50 CA090578